The effects of HSP72 expression on adhesion receptor activation and phagolysosome function in human PMNs (134.93)

Abstract

Abstract Heat shock protein 72 (HSP72) expression is a hallmark of functionally suppressed neutrophils from pediatric burn patients. CD11b and CD15 are critical receptors that mediate neutrophil (PMN) adhesion. In this study, we examined the effects of HSP72 on these receptors as well as phagolysosome function. Expression of CD11b, CD15 and pHrodo were measured by flow cytometry. HSP72 expression in PMNs, induced by 60-90 min incubation at 42C, suppressed the upregulation of high affinity CD11b conformation induced by fMLP (~90% reduction vs controls). Additionally, CD15 expression is reduced in HSP72 positive PMNs. GM-CSF treatment (5-25 ng/ml) appears to have a modest ability to preserve PMN function in stressed PMNs. HSP72 positive PMNs also have a reduced capacity phagocytose. Opsonized pHrodo labelled Staphylococcus aureus were incubated with HSP72 positive or negative PMNs. Control samples had significantly more pHrodo positive bacteria (~2-fold increase, controls vs stressed PMNs, P<0.01) than the thermally stressed cells. However, the HSP72 positive PMNs appeared to acidify phagolysosomes to the same extent as control PMNs. Taken together, these data suggest that HSP72 expression reduces adhesion as well as the extent of phagocytosis. These deficits may contribute to the immune suppression found in thermally injured patients. Supported by Shriners of North America.