The complement in milk and defense of the bovine mammary gland against infections

Abstract

-The mammary gland of dairy cows, which is prone to infection by various bacteria, mobilizes local and systemic immune defenses to cope with pathogens. The complement system plays an important part in the innate immunity against microorganisms through its bactericidal, opsonic, and phlogistic functions. The amount of the complement in the milk of healthy glands of dairy cows is low. Moreover, the classical pathway of activation is not functional because of a shortage in C1q. By contrast, the alternative pathway is active, deposits C3b and C3bi on bacteria, and generates amounts of C5a which are highly variable among cows. A slight inhibition of the bactericidal/hemolytic activities, of the deposition of C1q on bacteria, and of the phlogistic activity of C5a makes milk a rather anti-inflammatory fluid. The inhibitory activity does not involve C3b/ C3bi deposition on bacteria, nor the generation of C5a by the alternative pathway. When inflammation develops, the blood-derived complement components overcome the inhibitions and complement-dependent bactericidal, opsonic and phlogistic activities may be high in milk. Further research is necessary to evaluate the contribution of C5a to the recruitment of leukocytes in the mammary gland, and to specify the links between the complement system and the response of resident cells (leukocytes and mammary epithelial cells) to infection stimulus. This will help to define the contribution of the complement system to resistance against mastitis, and could help to differentiate animals more or less resistant to this frequent and costly disease.

Effect of Carprofen Treatment Following Experimentally Induced Escherichia coli Mastitis in Primiparous Cows

“…The marked difference in the onset of carprofen effects on chemotactic agents IL-8 and C5a could be explained by the location of mediator production. Interleukin-8 is directly produced by the epithelial cells in the mammary gland (Baggiolini and Clark-Lewis, 1992;Barber and Yang, 1998), whereas the bulk of C5a precursors are obtained from the blood through leakage of the disintegrated blood-milk barrier (Rainard et al, 1998;Rainard, 2003).…”

Host-defence-related proteins in cows’ milk

“…Lysozyme, lactoferrin and lactoperoxidase each possess the ability to suppress the growth of certain bacteria and were identified as minor milk proteins in the early part of the twentieth century . More recently, it has become apparent that milk also contains a range of additional antimicrobial proteins and peptides, including members of the b-defensin, complement, cathelicidin and S100 calgranulin families, as well as several acute phase proteins (Eckersall et al, 2001;Jia et al, 2001;Rainard, 2003;Swanson et al, 2004;Murakami et al, 2005;Lutzow et al, 2008). The role that two of these effector proteins play in contributing to the host-defence function of milk is described below, drawing on previously published work as well as our own unpublished data.…”

Innate immunity of the bovine mammary gland

“…The contribution of the complement system to the defense of the bovine mammary gland has recently been reviewed 372 P. Rainard, C. Riollet [142]. Complement is present in milk of healthy uninflamed glands at low but significant concentrations.…”

“…Deposition of the complement cleavage product C3b and its transformation into C3bi on bacteria favors their recognition by phagocytes through binding to the receptors CR1 and CR3, respectively [127]. Exudation of plasma provides the complement components which are absent in normal milk (in particular C1q), making possible the functioning of the classical pathway of activation, and the increase in the concentration of C3 augments the deposition of opsonic C3 fragments [142,144]. There is a temporally coincident increase in the BSA milk concentration and the generation of C5a in milk of E. coli mastitis [6,170].…”