Abnormalities of polymorphonuclear leukocyte function associated with a heritable deficiency of high molecular weight surface glycoproteins (GP138): common relationship to diminished cell adherence.

Abstract

Abs sbtract. Investigations ofpolymorphonuclear leukocyte (PMN) function were performed in a 5-yr-old white female with delayed umbilical cord separation, impaired pus formation, and a severe defect of PMN chemotaxis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated an almost total deficiency of a high molecular weight glycoprotein(s) (GP1 38)

Manifestations of Inflammatory Arthritis Are Critically Dependent on LFA-1

“…The leukocyte adhesion deficiency-I phenotype in humans and cattle (8,9,(42)(43)(44), as well as the defective T cell function and spontaneous skin ulceration seen in CD18 null mice emphasize that ␤ 2 integrins are critically important for host defense. Although LFA-1-deficient mice have deficits in experimental tumor models and increased mortality to gram (ϩ) sepsis with Streptococcus pneumoniae, they exist without apparent spontaneous illness in conventional mouse housing facilities (45,46).…”

“…Patients deficient in ␤ 2 integrin expression (the leukocyte adhesion deficiency-I phenotype) display leukocytosis, impaired wound healing, and particular susceptibility to recurrent microbial infection due in part to an inability to recruit leukocytes from the circulation and form pus (8,9). Mice deficient in CD18 (10) display a similar phenotype, with leukocytosis and susceptibility to bacterial infection (reviewed in Ref.…”

Neutrophil integrin affinity regulation in adhesion, migration, and bacterial clearance

“…Neutrophils from LAD-I patients were defective in phagocytosing C3-opsonized bacteria, whereas uptake of IgG opsonized pathogens was largely unaffected. 46 Stimulation of neutrophils enhances their phagocytic capacity, which was largely dependent on switching β 2 -integrins into an active confirmation, a mechanism known to be defective for neutrophils from patients with LAD-1. 47 It is expected that neutrophils from LAD-III patients are impaired for iC3b-mediated phagocytosis.…”

The adhesion molecules of inflammation

“…Although these patients had a persistent leukocytosis, very few leukocytes accumulated at infected, necrotic lesions. In 1984 several groups demonstrated that these patients' leukocytes were missing CDt la,b,c/CD18 and subsequent work has demonstrated that the primary genetic defects are in CD18, the shared subunit (2)(3)(4)(5)23,24). Thus, the inability of leukocytes to adhere to endothelium or other particles because of an inherited defect in adhesive molecules prevents accumulation of leukocytes at sites of microbial invasion and results in severe, recurrent infections.…”