Surfactant Protein D Enhances Phagocytosis and Killing of Unencapsulated Phase Variants of<i>Klebsiella pneumoniae</i>

Ofek, Itzhak; Mesika, Adi; Kalina, Moshe; Keisari, Yona; Podschun, Ranier; Sahly, Hany; Chang, Donald; Mcgregor, David K.; Crouch, Erika C.

doi:10.1128/iai.69.1.24-33.2001

Cited by 102 publications

(101 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The ability of bacteria to survive within the macrophages was quantified using a tetrazolium dye reduction assay as described elsewhere (18,19) and results are expressed as the percentage of survival of phagocytosed bacteria.…”

Section: Tetrazolium Dye Reduction Assay Of Bacterial Killingmentioning

confidence: 99%

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Aronoff

Peres

Serezani

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

PGI2 (prostacyclin) is a lipid mediator with vasodilatory and antithrombotic effects used in the treatment of vasoconstrictive/ischemic diseases including pulmonary artery hypertension. However, emerging research supports a role for PGs, including PGI2, in the regulation of both innate and acquired immunity. As PGI2 is unstable, we sought to define the effects of various PGI2 analogs on resident alveolar macrophage (AM) and peritoneal macrophage (PM) innate immune functions. The effects of iloprost, carbaprostacyclin, and treprostinil on the regulation of phagocytosis, bacterial killing, and inflammatory mediator production were determined in both macrophage populations from rats. Iloprost failed to suppress AM functions to the same degree that it did in PMs, a characteristic shared by carbaprostacyclin. This difference reflected greater expression of the Gαs protein-coupled I prostanoid receptor and greater cAMP generation in PMs than AMs. Treprostinil inhibited phagocytosis, bacterial killing, and cytokine generation in AMs to a much greater degree than the other PGI2 analogs and more closely resembled the effects of PGE2. Studies with the E prostanoid (EP) 2 receptor antagonist AH-6809 and EP2-null macrophages indicated that this was due in part to the previously unknown ability of treprostinil to stimulate the EP2 receptor. The present investigation for the first time identifies differences in immunoregulatory properties of clinically administered PGI2 analogs. These studies are the first to explore the capacity of PGI2 to regulate bacterial killing and phagocytosis in macrophages, and our findings may hold important consequences regarding the risk of infection for patients receiving such agents.

show abstract

Section: Tetrazolium Dye Reduction Assay Of Bacterial Killingmentioning

confidence: 99%

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Aronoff

Peres

Serezani

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…This assay was performed as described previously (61). Briefly, alveolar macrophages were isolated from BAL fluid from septic WT and IRAK-M -/-animals and counted and assessed for viability using Trypan blue exclusion.…”

Section: Methodsmentioning

confidence: 99%

Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M

Deng

Cheng

Newstead

et al. 2006

Journal of Clinical Investigation

166

252

View full text Add to dashboard Cite

Sepsis results in a state of relative immunosuppression, rendering critically ill patients susceptible to secondary infections and increased mortality. Monocytes isolated from septic patients and experimental animals display a "deactivated" phenotype, characterized by impaired inflammatory and antimicrobial responses, including hyporesponsiveness to LPS. We investigated the role of the LPS/TLR4 axis and its inhibitor, IL-1 receptor-associated kinase-M (IRAK-M), in modulating the immunosuppression of sepsis using a murine model of peritonitis-induced sepsis followed by secondary challenge by intratracheal Pseudomonas aeruginosa. Septic mice demonstrated impaired alveolar macrophage function and increased mortality when challenged with intratracheal Pseudomonas as compared with nonseptic controls. TLR2 and TLR4 expression was unchanged in the lung following sepsis, whereas levels of IRAK-M were upregulated. Macrophages from IRAK-M-deficient septic mice produced higher levels of proinflammatory cytokines ex vivo and greater costimulatory molecule expression in vivo as compared with those of their WT counterparts. Following sepsis and secondary intrapulmonary bacterial challenge, IRAK-M -/-animals had higher survival rates and improved bacterial clearance from lung and blood compared with WT mice. In addition, increased pulmonary chemokine and inflammatory cytokine production was observed in IRAK-M -/-animals, leading to enhanced neutrophil recruitment to airspaces. Collectively, these findings indicate that IRAK-M mediates critical aspects of innate immunity that result in an immunocompromised state during sepsis.

show abstract

“…Numerous studies have examined the roles of SP-A and SP-D as opsonins and their participation in pathogen phagocytosis (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Most often, increased phagocytosis of opsonized pathogens is beneficial to the host as a mode of clearance.…”

Section: Roles Of Sp-a/-d In Cell-mediated Immunitymentioning

confidence: 99%

Eosinophil-Associated Lung Diseases. A Cry for Surfactant Proteins A and D Help?

Ledford

Addison

Foster

et al. 2014

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Surfactant proteins (SP)-A and SP-D (SP-A/-D) play important roles in numerous eosinophil-dominated diseases, including asthma, allergic bronchopulmonary aspergillosis, and allergic rhinitis. In these settings, SP-A/-D have been shown to modulate eosinophil chemotaxis, inhibit eosinophil mediator release, and mediate macrophage clearance of apoptotic eosinophils. Dysregulation of SP-A/-D function in eosinophil-dominated diseases is also not uncommon. Alterations in serum SP-A/-D levels are associated with disease severity in allergic rhinitis and chronic obstructive pulmonary disease. Furthermore, oligimerization of SP-A/-D, necessary for their proper function, can be perturbed by reactive nitrogen species, which are increased in eosinophilic disease. In this review, we highlight the associations of eosinophilic lung diseases with SP-A and SP-D levels and functions.

show abstract

Surfactant Protein D Enhances Phagocytosis and Killing of Unencapsulated Phase Variants ofKlebsiella pneumoniae

Abstract: Pulmonary surfactant protein D (SP-D) is a collagenous C-type lectin (collectin) that is secreted into

Cited by 102 publications

References 65 publications

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Synthetic Prostacyclin Analogs Differentially Regulate Macrophage Function via Distinct Analog-Receptor Binding Specificities

Sepsis-induced suppression of lung innate immunity is mediated by IRAK-M

Eosinophil-Associated Lung Diseases. A Cry for Surfactant Proteins A and D Help?

Contact Info

Product

Resources

About