Activation of complement system by porins extracted from Salmonella typhimurium

Abstract

The effect of porins purified from Salmonella typhimurium on the complement system was investigated both in vitro and in vivo. Incubation of porins with either human or guinea pig serum resulted in the consumption of the total complement activity when an amount of porins ranging from 8 to 10 ,ug per 100 ,ld of serum was used. The activation of the complement system was temperature dependent, suggesting an active process rather than passive adsorption of the complement components by porins. In addition, the activation had a fast kinetic and proceeded mainly through the classical pathway. This conclusion is supported by the consumption of Cls and C4 in normal human serum treated with porins and also by the depletion of C3 activity in the Cls-deficient serum which was marked only when purified Cls was added to the serum before incubation with porins. Injection of 100 ,ug of porins into guinea pigs induced profound complement consumption at 6 h postinjection that persisted up to 12 h. We conclude from this study that porins can effectively contribute to complement activation and to subsequent biological events induced by gram-negative bacteria.

Inflammatory effects of Salmonella typhimurium porins

“…This evidence of proinflammatory activity by porins further enlarges the field of action of protein-host interactions. These proteins intervene in nonspecific host defenses (4,9,29) and, as a consequence, in the specific immunologic response (27). Among surface components, therefore, porins can be considered another surface molecule, in addition to LPS, that may be an important inducer of biological activity in interactions with the host.…”

“…These proteins, therefore, induce the activation of the complement system by acting both on the classic pathway and on the alternative pathway (9); they bind to human polymorphonuclear leukocytes, decreasing some of their biological functions (29), and act as mitogens for B lymphocytes (24,27). Furthermore, in rats the porins increase the toxicity of cardiotoxic molecules (8) and damage renal tubules (28).…”

Induction of tyrosine phosphorylated proteins in THP-1 cells by Salmonella typhimurium, Pasteurella haemolytica and Haemophilus influenzae porins

“…Porins of Salmonella typhimurium have endotoxin-like e¡ects such as lethal action, the ability to elicit a local Shwartzman reaction and pyrogenicity [10]. S. typhimurium porins also activate the complement system in vitro and in vivo [11]. Furthermore, the porins have the ability to stimulate pro-and anti-in£ammatory cytokine synthesis and release [12^14].…”

Priming of T‐Cell Responses in Mice by Porins of Salmonella typhimurium

“…Several workers have demonstrated porins to be important antigens, which elicit CMI responses through a delayed-type hypersensitivity reaction, interleukin-2 (IL-2) and interferon-g (IFN-g) production, and mitogenic effects on T and B cells [4,10]. Porins also activate the complement system and contribute to the pathogenesis of the bacterial infection [11,12]. Recently, we have demonstrated that significant lymphoproliferation could be obtained by immunization with porins.…”