Fibrinogen-neutrophil interactions in response to fMLP and XXXX fimbrial peptides.

@entity1 @entity32 @entity14915 @entity7278 @entity535 @entity5037 @entity2823 @entity2523
@entity2523 (P.g) is the primary bacterial agent in many forms of @entity7278 . Since polymorphonuclear leukocytes (PMNs) are first-line responders to P.g.- induced @entity32 , and fibrinogen is important for in vivo PMN in this disease, we have studied the effect of @entity5037 ( @entity14915 ) (an inflammatory stimulus), P.g. fimbriae and fimbrial peptides (based on FimA, the main structural protein of P.g. fimbriae) on PMN-fibrinogen interactions. Freshly isolated @entity1 PMNs were allowed to react with @entity2823 -Fibrinogen and various fimbrial peptides (denoted as FimA followed by @entity535 number within whole FimA protein), and @entity2823 -Fibrinogen binding was measured using flow cytometry. Freshly isolated neutrophils were also challenged with Fibrinogen and/or fimbrial peptides to measure IL-8 secretion using ELISA. Our studies show that fibrinogen binding to PMNs is enhanced (p < 0.01) in response to fMLP as well as fimbrial peptides (FimA 61-80) containing the motif LTTE (p < 0.01) in a dose dependent manner but not in response to peptides without that motif. We also observed that fMLP and FimA 61-80 have an additive effect on fibrinogen binding to PMNs (p < 0.05), and fMLP and FimA 171-185 significantly inhibit fMLP-induced fibrinogen binding (p < 0.01). To determine of the role of inflammatory cytokines, we examined IL-8 release from PMNs in response to combinations of @entity2523 fimbriae, fMLP and fibrinogen. In all cases, IL-8 release increased in a dose-dependent manner (p < 0.05). fMLP-fibrinogen effect on IL-8 release from PMNs was synergistic while fimbriae-fibrinogen effect was additive. In summary, PMN priming by fimbrial peptides facilitates fibrinogen-PMN interaction and may increase @entity32 .
