Monocyte derived neutrophil chemotactic factor

Yoshimura T, Matsushima K, Tanaka S, et al. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A 1987 84 9233-9237. 

Djeu, J. Y., Matsushima, K., Oppenheim, J. J., Shiotsuki, K., Blanchard, D. K. (1990). Functional activation of human neutrophils by recombinant monocyte-derived neutrophil chemotactic factor/IL-8. J. Immunol. 144, 2205-10. 

Based on the fact that interleukin-1 (IF-1) induces migration of leukocytes to sites of injection, IF-1 was thought to have chemotactic activity. In fact, leukocyte-derived chemoattractants for phagocytic cells were present in partially purified preparations of IF-1 (Fuger et al, 1983 Sauder et al, 1984). However, when purified to homogeneity, IF-1 lost its chemotactic activity. Further studies revealed that the partially purified IF-1 preparations were contaminated with both a chemotactic factor for monocytes and a monocyte-derived neutrophil chemotactic factor, termed MDNCF (Yoshimura et al, 1987, 1989 Matsushima et al, 1988, 1989). These paradoxical observations were resolved by data showing that IF-1 was a potent inducer of these chemotactic factors. The same mononuclear cell-derived neutrophil attrac-tants were also identified by several other laboratories of (Schroder et al, 1987 Walz et al, 1987). Eater, Farsen et al (1989) reported that MDNCF was chemotactic for T lymphocytes as well as neutrophils, and, based on the presumed involvement of MDNCF in the immune response, it was renamed IF-8 (Farsen et al, 1989 Oppenheim et al, 1991). 

Matsushima, K., Morishita, K., Yoshimura, T., Lavu, S., Kobayashi, Y., Lew, W., Appella, E., Kung, H. F., Leonard, E., and Oppenheim, J. J. (1988). Molecular cloning of cDNA for a human monocyte derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCE mRNA by interleukin 1 and tumor necrosis factor. J. Exp. Med. 167, 1883-1893. 

Matsushima K, Morishita K, Yoshimura T, Leonard E, Oppenheim JJ. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin-1 and tumor necrosis factor. J Exp Med 1988 167 1883-1893. 

But in reality, chemokines, the proteins that are the chemical messengers between cells and the immune system, attracted and retained the attention of biologists long before this time. Actually, the first chemokine, human monocyte-derived neutrophil chemotactic factor or interleukin 8 (IL-8), was identified in 1987 (2). Since then, scores of chemokines and their receptors have been identified, and we know they are prominent players in lung defense against infection. 

Terkeltaub, R., Zachariae, C., Santoro, D., Martin, J., Peveri, P., and Matsushima, K. (1991) Monocyte-derived neutrophil chemotactic factor/interleukin-8 is a potential mediator of crystal-induced inflammation. Arthritis Rheum. 34,894-903. 

Figure 4.8. Hypothesis for the local generation of mast-cell-stimulating peptides by the action of neutrophil-derived enzymes on albumin. Initial stimulation of the mast cell by any of a variety of agents causes the release of preformed histamine (H) neutrophil and eosinophil chemotactic factors (NCF, ECF) and enzymes and the de novo synthesis of prostaglandins (PG) and leukotrienes (LT). These agents increase vascular permeability and vessel diameter. As a result, albumin and later neutrophils (PMN) enter the tissue space where the latter undergo phagocytosis and the secretion of proteolytic enzymes to the extracellular space where they act on albumin to generate NRP (neurotensin-related peptide) and HRP (histamine-releasing peptide). These newly formed peptides then act as a second stimulus to the mast cell. In addition NRP and HRP may affect other immunocompetent celt such as monocytes, macrophages or eosinophils.

Cliuical pharmacology Native PDGF is a growth factor derived from blood platelets that mediates tissue repair. Becaplermin has biological activity similar to that of endogenous PDGF it promotes the chemotactic recruitment and prohfera-tion of cells involved in wound repair— fibroblasts, smooth muscle cells, monocytes, and neutrophils—and enhances the formation of granulation tissue. 

Colditz, I., Zwahlen, R., Dewald, B., and Baggiolini, M. (1989) In vivo inflammatory activity of neutrophil-activating factor, a novel chemotactic peptide derived from human monocytes. Am. J. Pathol. 134, 755-760. 

The concept of leukocyte-specific chemoattractants was enunciated almost as soon as microscopy revealed the existence of leukocyte-specific inflammatory infiltrates (I). With the advent of reproducible in vitro chemotaxis assays, evidence for the existence of chemoattractants was bolstered by activities found in crude biological preparations. For example, the monocytic infiltrates associated with a wide variety of tumor types were suggested to be elicited by a tumor-derived chemotactic factor (TDCF) that could attract monocytes to the exclusion of neutrophils (2). In the late 1970s and early 1980s, a monocyte-specific chemoattractant activity could be demonstrated in medium conditioned by malignant cell lines whose cognate tumors were associated with monocytic infiltration in vivo (2-4). 

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