Dynamic expression of the signal regulatory protein alpha and CD18 on porcine PBMC during acute endotoxaemia.

Endotoxaemia elicits a massive inflammatory insult affecting the beta2 integrin CD18. Being an adhesion molecule, CD18 is pivotal in inflammation and, moreover, exiting data suggest that CD18 is a lipopolysaccharide (LPS) receptor. Early LPS-induced inflammation is regulated by the signal regulatory protein (SIRPalpha), which is identical to the porcine panmyelocytic marker swine CD workshop 3 (SWC3), and LPS-induced downregulation of SIRPalpha has been described in vitro. The dynamic SIRPalpha/SWC3 and CD18 expression on peripheral blood mononuclear cells (PBMC) in vivo during LPS-induced inflammation is the focus of this study. Pigs were randomized into LPS (n = 12) or control (n = 6) groups. At start 0 min, LPS infusion was stepwise (2.5-15 mug/kg/h, 30 min) followed by maintenance infusion (2.5 mug/kg/h, 330 min). PBMC were isolated at 0, 60, 240 and 360 min, and two-colour flow cytometry was performed using monoclonal antibodies identifying SWC3 and CD18. Viability was tested using 7-amino-actinomycin D. LPS dramatically changed the relative distribution of circulating myeloid cells. At 60 min monocytes disappeared. This was followed by reappearance of a distinct population with low CD18 and SIRPalpha/SWC3 expression. Cell sorting showed that the appearing population comprised band neutrophils and apoptotic/dead cells. The remaining monocytes expressed less CD18 at 360 min than the controls (P = 0.03). The appearance of a distinct cell population comprising apoptotic cells and band neutrophils consistent with LPS-induced apoptosis, and decreased CD18 expression on monocytes suggests that early CD18 downregulation is profitable for the host in a situation with an intense LPS stimulus.

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