Species Variation in Neutrophil Biochemistry and Function

Abstract Polymorphonuclear neutrophils are essential to host defense against bacterial infection. They are also used as readily available cells for study of general processes of cell biology including receptor regulation, ion transport, and cellular activation. Studies of host defense functions and cell activation processes frequently employ neutrophils from mice, rabbits, or guinea pigs with an explicit or implicit extrapolation to the human situation; conversely, attempts to understand the pathophysiology of veterinary infections may rely upon information derived from studies with human neutrophils. Indeed, some studies of neutrophil physiology and function require close scrutiny of the methods to disclose which species is being examined. The relevance of studies of neutrophils from one species to disease in another species obviously depends upon the degree to which the basic physiologic processes are comparable. However, this comparability can be very difficult to determine. Most studies of neutrophil physiology and function use cells from only a single species, and differences in collection, isolation, and processing complicate any attempt at comparison of different studies. Whenever an animal model is used to study the pathogenesis of human infection or to justify clinical trials of antimicrobial therapy, tacit assumptions are made about the nature of the host response. Among these assumptions is that neutrophil response in the animal model is analogous to that in the human or that responses of other species are equivalent. While this may be generally true as a first approximation, there are circumstances in which it may be misleading. There are marked species variations in distribution of lysosomal enzymes [31] which could affect activity against specific microorganisms, and these variations could affect both the vulnerability of the species to a given infection and the response of the organism to antibiotics. Neutrophils from some species do not respond to agents such as leukotriene B4 and formyl methionyl leucyl phenylalanine (Fmlp) which are potent chemoattractants for other species [19], a difference which suggests that studies of the inflammatory process in one species may have limited relevance to others. Even apparently analogous genetic abnormalities of neutrophils may not produce analogous susceptibility to infections in different species [69]. Appreciation of interspecies differences is important to the interpretation and appropriate application of in vitro and in vivo studies of both pathogenesis and therapeutic interventions. Remarkably little attention has been devoted to detailed direct comparisons of neutrophils from different species. Because such comparisons are potentially important to an understanding of basic pathophysiology and to clinical problems in both human and veterinary practice, we set out to assess currently available information on similarities and differences between the biochemical and functional capacities of neutrophils from different mammalian species. While such a survey cannot pretend to be all-inclusive, an overview of major comparative studies can provide a context for judgment of newer information in the area.