Human platelets efficiently kill IgG-opsonized<i>E. coli</i>

Riaz, Anum H.; Tasma, Brian E.; Woodman, Michael E.; Wooten, R. Mark; Worth, Randall G.

doi:10.1111/j.1574-695x.2012.00945.x

Cited by 39 publications

(49 citation statements)

References 28 publications

(44 reference statements)

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“…Aggregated IgGs [16] Mouse anti-human platelet mAb [30] Influenza virus H1N1 [16] Influenza virus H1N1 [16] Aggregated IgGs [16] HIT ICs [100] Anti-CD40L mAb + CD40L [75] Aggregated IgGs [19] IgG-coated beads [18] Escherichia coli [69] Fig. 3.…”

Section: Arachidonic Acid Metabolism (Thromboxane Production)mentioning

confidence: 99%

Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis

Arman

Krauel

2015

Journal of Thrombosis and Haemostasis

112

105

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Summary Beyond their prominent role in hemostasis and thrombosis, platelets are increasingly recognized as having immunologic functions. Supporting this, human platelets express FcγRIIA (CD32a), a low‐affinity Fc receptor (FcR) for the constant region of IgG that recognizes immune complexes (ICs) and IgG‐opsonized cells with high avidity. In leukocytes, FcγRIIA engagement initiates strong effector functions that are key for immune and inflammatory responses, including cytokine release, antibody‐dependent cell‐mediated killing of pathogens, and internalization of ICs. However, the physiologic relevance of platelet‐expressed FcγRIIA has received little attention in previous reviews on FcRs. This article summarizes and discusses the available information on human platelet FcγRIIA. The importance of this receptor in heparin‐induced thrombocytopenia, a prothrombotic adverse drug effect, is well documented. However, studies demonstrating platelet activation by IgG‐opsonized bacteria point to the physiologic relevance of platelet FcγRIIA in immunity. In this context, platelet activation and secretion may facilitate both a direct antimicrobial function of platelets and crosstalk with other immune cells. Additionally, a role for platelet FcγRIIA in IgG‐independent hemostasis and physiologic thrombosis, by means of amplifying integrin αIIbβ3 outside‐in signaling, has also been proposed. Nonetheless, the thrombotic complications found in some infective and autoimmune diseases may result from unbalanced FcγRIIA‐mediated platelet aggregation. Moreover, FcγRIIA is not expressed in mice, and thrombocytopenia and/or thrombotic events found after drug administration can only be recapitulated by the use of human FcγRIIA‐transgenic mice. Altogether, the available data support a functional role for platelet FcγRIIA in health and disease, and emphasize the need for further investigation of this receptor.

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Section: Arachidonic Acid Metabolism (Thromboxane Production)mentioning

confidence: 99%

Human platelet IgG Fc receptor FcγRIIA in immunity and thrombosis

Arman

Krauel

2015

Journal of Thrombosis and Haemostasis

112

105

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“…Platelets also bind various pathogens, including HIV and Staphylococcus aureus . Although not considered to be professional phagocytes, platelets are capable of internalizing targets, resulting in the killing of various bacterial species, including Escherichia coli and S. aureus . In addition to their direct bactericidal activities, platelets can affect both innate and adaptive immune responses through interactions with various types of leukocytes, most notably neutrophils .…”

Section: Introductionmentioning

confidence: 99%

A novel conditional platelet depletion mouse model reveals the importance of platelets in protection against Staphylococcus aureus bacteremia

Wuescher

Takashima

Worth

2015

Journal of Thrombosis and Haemostasis

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Background Platelets are critical cells for maintaining vascular hemostasis but their activities in other processes are becoming apparent. Specifically, the ability of platelets to recognize and respond to infectious agents is an important area of investigation. To understand the physiological roles of platelets in vivo, most researchers have used antibody-mediated platelet depletion, which has certain limitations. Objective To develop an optimal system to study the contribution of platelets to protection from S. aureus blood infection. Methods Here we describe a novel experimental model of conditional platelet depletion based on the Cre-recombinase cell ablation system. Using this technology, the simian diphtheria toxin receptor was expressed in platelet factor 4 (PF4) positive cells (megakaryocytes and platelets). Results Systemic administration of diphtheria toxin (DT) every 48 hours results in reduced platelet numbers that become undetectable after six days. While platelets are depleted, no other blood cells are affected. Using this newly-developed model, the functional contributions of platelets in protection against Staphylococcus aureus (S. aureus) bacteremia was examined. Platelet-depleted mice succumbed to infection more rapidly than wild-type (WT) mice and contained significantly higher bacterial burden in kidneys, increased serum markers of kidney damage and elevated levels of cytokines indicative of septic shock. Conclusions Here we illustrate a new mouse model for conditional platelet depletion and implicate platelets as important participants of the immune response to bacterial blood infections.

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“…The combined importance of platelet FcγRIIA and anti‐PF4/P IgG is further clear from work by Riaz et al ., who reported that both unopsonized and IgG‐opsonized E. coli bacteria could associate with platelets, but only IgG‐opsonized E. coli were efficiently killed by platelets . The bactericidal activity was dependent on FcγRIIA, was sensitive to cytochalasin D and was not a result of reactive oxygen metabolites.…”

Section: The Fcγriia and Platelet–bacteria Interactionsmentioning

confidence: 99%