Differential phosphorylation of the β2 integrin CD11b/CD18 in the plasma and specific granule membranes of neutrophils

Buyon, Jill P.; Philips, Mark R.; Merrill, Joan T.; Slade, Seth G.; Leszczynska-Piziak, Joanna; Abramson, Steven B.

doi:10.1002/jlb.61.3.313

Cited by 21 publications

(14 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to particular kinases regulating L-selectin shedding, phosphorylation levels may be modulated by phosphatases as well. For instance, Buyon et al [54] have demonstrated that granuleassociated phosphatases affect the levels of CD11b/CD18 phosphorylation. Future studies in our laboratory will evaluate the role of phosphatase in influencing the kinetics of L-selectin shedding.…”

Section: Discussionmentioning

confidence: 99%

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Alexander

Kishimoto

Walcheck

2000

Journal of Leukocyte Biology

View full text Add to dashboard Cite

The signaling factors that direct the rapid shedding of L-selectin from neutrophils upon chemoattractant stimulation are poorly understood. Protein kinase C (PKC) has been implicated, yet previous studies have relied on the use of phorbol esters and nonselective kinase inhibitors. We treated neutrophils with various selective kinase inhibitors to evaluate their effects on N-formylmethionyl-leucyl-phenylalanine (fMLP)-induced Lselectin shedding. We found that three selective inhibitors of PKC, structurally related to staurosporine, largely blocked both fMLP-and phorbol 12-myristate 13-acetate (PMA)-induced L-selectin shedding; however, these inhibitors did not affect fMLP-induced up-regulation of Mac-1 (CD11b/ CD18) expression, which has been shown not to involve PKC. Other selective serine, threonine, and tyrosine kinase inhibitors were found not to block fMLP-induced L-selectin shedding. These findings provide more definitive evidence for the role of PKC in chemoattractant-induced L-selectin proteolysis. It is interesting that certain highly selective PKC inhibitors, not structurally related to staurosporine, were found to directly induce Lselectin shedding from neutrophils. J. Leukoc. Biol. 67: 415-422; 2000.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Alexander

Kishimoto

Walcheck

2000

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…As we know, CD11a is constitutively expressed on PMN surface, whereas other adhesive molecules (CD11b and CD11c) can be taken out from intracellular storage pools situated in 3 mobilizable organelles (specific granules, gelatinase granules, and secretory vesicles). 38,39 We must remember the role played by endocytosis mechanisms in regulating leukocyte adhesiveness. A mechanism of internalization, in fact, has been demonstrated, especially after activation with PMA, for CD18 and CD11b but not for CD11a.…”

Section: Discussionmentioning

confidence: 99%

“…It must be also pointed out that granulocyte activation is accompanied by the integrin phosphorylation 39 that affects only the plasma membrane-associated molecules and not the presynthesized intracytoplasmic reserves; an altered integrin phosphorylation/dephosphorylation balance, related to the PMN spontaneous activation, might explain the decrease of the phenotypical expression of CD11a that cannot be taken back into storage pool.…”

Section: Discussionmentioning

confidence: 99%

Polymorphonuclear Integrins, Membrane Fluidity, and Cytosolic Ca ²⁺ Content After Activation in Essential Hypertension

et al. 2000

View full text Add to dashboard Cite

Abstract-The purpose of this research was to obtain further information about the role of polymorphonuclear leukocytes in essential hypertension. These cells could be involved in the pathogenesis of organ injury. Thirty subjects (14 men and 16 women) with essential hypertension were enrolled. In these subjects we determined, at baseline and after in vitro activation with 4-phorbol 12-myristate 13-acetate and N-formyl-methionyl-leucyl-phenylalanine, the polymorphonuclear leukocyte membrane fluidity, obtained by labeling the cells with 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene, cytosolic Ca 2ϩ concentration, obtained by marking the cells with Fura 2-AM, and integrin pattern (CD11a, CD11b, CD11c, and CD18), by using the indirect immunofluorescence with a flow cytometer. At baseline there was no difference in membrane fluidity between normal subjects and hypertensives, whereas hypertensives showed an increase in cytosolic Ca 2ϩ content and an increase of the phenotypical expression of CD11a, CD11b, and CD18. In normal subjects and in hypertensives, after activation, no variation was found in membrane fluidity and cytosolic Ca 2ϩ content. In normal subjects, after activation, we observed a significant increase of the expression of all adhesion molecules, whereas in hypertensives we found an increase of the expression of CD11b, CD11c, and CD18 but also a decrease of CD11a. The behavior of the polymorphonuclear leukocyte integrin profile may have several explanations, and in particular, the trend of CD11a after chemotactic activation may be related to its cleavage or to an altered integrin phosphorylation/dephosphorylation balance hypothetically present in this clinical condition. Key Words: hypertension, essential Ⅲ neutrophils Ⅲ integrins Ⅲ membranes Ⅲ calcium I n recent years, the knowledge about hypertensive disease was enriched by much evidence regarding the role of circulating leukocytes. In fact, from observations of an altered leukocyte count in experimental and clinical hypertension, 1-5 some authors hypothesized that leukocytes could be activated and that this condition, strengthened by nitrobule tetrazolium (NBT) reduction test, could contribute to explaining organ injury. 6 -11 In our previous works, 12,13 we evaluated, in essential hypertension, the leukocyte rheology, expressed as flow properties, polymorphonuclear leukocyte (PMN) membrane fluidity and PMN cytosolic Ca 2ϩ content at baseline and after chemotactic activation.Subsequently, our aim was to examine, in hypertensives, the PMN adhesion molecule profile. Our interest in this topic, for which there is little information in the literature, is derived from the fact that some experimental data underline how in this clinical condition an abnormality of the leukocyte adhesion is present. 9 -11,14 As we know, adhesion is particularly mediated by integrins; among these, ␤ 2 integrins (CD11a, CD11b, CD11c, CD18) are very important.Integrins 15,16 are usually in a low-affinity state that makes them unable to interact with their corresponding...

show abstract

“…Taken together with our findings in transfected COS-7 cells, these results indicate that the patient's PMN Mac-1, including that translocated from storage compartments, is as effective as wild-type Mac-1 in ligand binding. Studies by Buyon et al 40 indicating that phosphorylation of Mac-1 occurs at the plasma membrane but not in specific granule membranes showed further that chemoattractant stimulation (fMLF) resulted in phosphorylation of only the ␣ M subunit and not the ␤ 2 subunit. This is consistent with our findings of normal activation of the patient's PMN Mac-1 by fMLF stimulation, in that loss of most of the ␤ 2 cytoplasmic domain might be predicted to have no discernible effect under these conditions.…”

Section: Discussionmentioning

confidence: 99%

Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1

Hixson

Smith

Shurin

et al. 2004

Blood

View full text Add to dashboard Cite

Two novel CD18 mutations were identified in a patient who was a compound heterozygote with type 1 leukocyte adhesion deficiency and whose phenotype was typical except that he exhibited hypertrophic scarring. A deletion of 36 nucleotides in exon 12 (1622del36) predicted the net loss of 12 amino acid (aa) residues in the third cysteine-rich repeat of the extracellular stalk region (mut-1). A nonsense mutation in exon 15 (2200G>T), predicted a 36-aa truncation of the cytoplasmic domain (mut-2). Lymphocyte functionassociated antigen 1 (LFA-1) and macrophage antigen-1 (Mac-1) containing the mut-1 ␤ 2 subunit were expressed at very low levels compared with wild-type (wt) ␤ 2 . Mac-1 and LFA-1 expression with the mut-2 ␤ 2 subunit were equivalent to results with wt ␤ 2 . Binding function of Mac-1 with mut-2 ␤ 2 was equivalent to that with wt ␤ 2 . However, binding function of LFA-1 with the mut-2 ␤ 2 subunit was reduced by 50% versus wt ␤ 2 . It was concluded that (1) the portion of the CD18 stalk region deleted in mut-1 is critical for ␤ 2 integrin heterodimer expression but the portion of the cytoplasmic domain truncated in mut-2 is not; and (2) IntroductionImportant insights related to the molecular mechanisms that determine ␤ 2 integrin structure and function have arisen from the study of naturally occurring mutations in the common ␤ 2 subunit of this integrin family. 1,2 A range of mutations in the CD18 gene have been identified in patients with leukocyte adhesion deficiency type 1 (LAD-1), including deletions, truncations, substitutions, frame shifts, and intronic mutations that result in abnormalities of the CD18 protein ranging from absence of protein product, deficient alpha-beta subunit association, and reduced protein size. 1,3-5 All such mutations have resulted in diminished expression of the CD18 integrins on leukocytes, and some mutations also have caused integrin dysfunction. 1,[3][4][5] Patients typically have recurrent bacterial or fungal infections of skin and mucous membranes, impaired mobilization of leukocytes to sites of infection, severe gingivitis/ periodontitis with permanent loss of dentition, and atrophic scarring of wounds. 1,2,6 Laboratory features include a pronounced leukocytosis in the absence of infection, reduced expression of all members of the CD18 or ␤ 2 integrin family on circulating leukocytes, and diminished CD18-dependent leukocyte functions, including cell adhesion, chemotaxis, transendothelial migration, and oxidative burst activation in response to iC3b-coated particles. 1,2,6 We have identified an adult male patient with LAD-1 whose clinical features resemble those of the moderate LAD-1 phenotype, except that his wounds heal with hypertrophic rather than atrophic scarring. His levels of CD18 integrin expression are higher than those of most other reported patients with the moderate phenotype of LAD-1, but the CD18-dependent functions of his leukocytes were similar to those of other moderate phenotype individuals. 1,7 He was found to be a compound heterozygote with 2 novel m...

show abstract

Differential phosphorylation of the β2 integrin CD11b/CD18 in the plasma and specific granule membranes of neutrophils

Abstract: Abstract:Neutrophil aggregation is mediated by the 132 U1t I fl

Cited by 21 publications

References 37 publications

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Polymorphonuclear Integrins, Membrane Fluidity, and Cytosolic Ca ²⁺ Content After Activation in Essential Hypertension

Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1

Contact Info

Product

Resources

About

Differential phosphorylation of the β2 integrin CD11b/CD18 in the plasma and specific granule membranes of neutrophils

Abstract: Abstract:Neutrophil aggregation is mediated by the 132 U1t I fl

Cited by 21 publications

References 37 publications

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Effects of selective protein kinase C inhibitors on the proteolytic down-regulation of L-selectin from chemoattractant-activated neutrophils

Polymorphonuclear Integrins, Membrane Fluidity, and Cytosolic Ca 2+ Content After Activation in Essential Hypertension

Unique CD18 mutations involving a deletion in the extracellular stalk region and a major truncation of the cytoplasmic domain in a patient with leukocyte adhesion deficiency type 1

Contact Info

Product

Resources

About

Polymorphonuclear Integrins, Membrane Fluidity, and Cytosolic Ca ²⁺ Content After Activation in Essential Hypertension