Human neutrophil responses to pathogenic Escherichia coli are receptor-specific and selectively augmented by recombinant human tumor necrosis factor-alpha.

Abstract

The effect of recombinant human tumor necrosis factor-alpha (rhTNF alpha) on neutrophil (PMNL) response to uropathogenic Escherichia coli was assessed. A strain expressing mannose-sensitive adhesins (type 1 fimbriae) stimulated significant primary granule, secondary granule, and leukotriene B4 (LTB4) release. The same strain grown to suppress fimbrial expression and three non-type 1-fimbriated strains stimulated only background low-level PMNL activation. The binding of the type 1-fimbriated strain to PMNL was inhibitable by D-mannose and concanavalin A, while that of non-type 1-fimbriated strains was not but was inhibited by antibodies to the PMNL complement receptors 1 and 3. TNF alpha (10(-9) M) synergistically augmented the non-type 1-fimbriated E. coli-stimulated LTB4 release and additively increased secondary granule release without affecting primary granule release. In contrast, none of the responses to the type 1-fimbriated strain were augmented by TNF alpha. In the absence of mannose-sensitive adhesins, the activation of PMNL by E. coli may involve both complement receptors 1 and 3 and be augmented by TNF alpha.