Early cells chemotaxis

Histamine was synthesized in 1907 and later isolated from mammalian tissues. Early hypotheses concerning the possible physiologic roles of tissue histamine were based on similarities between the effects of intravenously administered histamine and the symptoms of anaphylactic shock and tissue injury. Marked species variation is observed, but in humans histamine is an important mediator of immediate allergic (such as urticaria) and inflammatory reactions, although it plays only a modest role in anaphylaxis. Histamine plays an important role in gastric acid secretion (see Chapter 62) and functions as a neurotransmitter and neuromodulator (see Chapters 6 and 21). Newer evidence indicates that histamine also plays a role in chemotaxis of white blood cells. 

Early studies suggested that IL-1 and TNF were chemotactic for PMN. However, it has become apparent that this activity resides in a family of molecules of 10 kDa, called neutrophil activating peptides (NAP) or IL-8 (L15). IL-1 and TNF induce the release of these molecules from mononuclear cells, fibroblasts, endothelial cells, and keratinocytes and they act on a specific receptor expressed by PMN. The main activity ascribed to these molecules is PMN chemotaxis, but the molecules may cause oxygen radical and enzyme release by PMN and mobilize PMN into the circulation. The common feature that identifies members of this family of peptides is alignment of four cysteine residues. IL-8 is the most potent chemotactic member of this family. Synthesized as a 99-amino-acid precursor, lL-8 is released as a 79-amino-acid molecule, IL-8a, which itself is further cleaved to 77- and 72-amino-acid forms, IL-8P and IL-8y. IL-8y is predominantly found to be associated with macrophages and may reflect the proteolytic enzymes released by macrophages. Receptors for IL-8 have been identified on PMN and approximately 20% of lymphocytes. The three-dimensional structure of IL-8 (NAP-1) has been reported (C27). 

D. discoideum shows reliable chemotaxis to cAMP at the early development stage, after 5-h starvation. These cells are typically used for chemotaxis analysis. This section describes the method for preparing the cells. 

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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