Chemotactic Factor Activity Research Articles

Discussion paper: effect of supernatants from long-term lymphoid cell lines on metastatic cutaneous tumors following local injection.

A fraction with lymphokine properties was isolated from supernatant medium of the continuous cultured human lymphoblast cell line, 1788. Culture medium containing 2% human serum was used for cell growth in order to minimize antigenicity of supernatant fractions isolated from the medium. The culture medium was passed through an Amicon XM-100 membrane, concentrated over a PM-10 membrane, lyophilized, and reconstituted to a final concentration of approximately 40:1. Studies in vivo and in vitro showed that the active fraction contained skin reactive factor (when injected intradermally into guinea pigs and humans), lymphotoxin, migration inhibition factor, chemotactic factor, and macrophage activation factor. This same preparation, when injected intralesionally into cutaneous tumors, induced an inflammatory reaction followed by tumor regression. The fraction confined between membranes of pore size 10,000-100,000 daltons was active in promoting tumor regression, while the fraction less than 10,000 daltons was inactive. Patients with skin lesions from metastatic carcinoma of the breast and other malignancies were studied, and 16 out of 30 treated lesions were judged to have undergone either complete or greater than 50% regression. Of these, 8 were biopsied before and after lymphokine injection, and 6 out of 9 were negative for tumor cells. Additional studies in vitro with material fractionated on Sephadex G-200 indicated that the macrophage-activating component binds to alpha-2 macroglobulin in the culture medium.

5 - Leucocyte Chemotaxis: Physiological Considerations and Abnormalities

Expression of the inflammatory process is dependent on mobilisation of leucocytes, which require leucocyte chemotaxis. Recent technological advances have enabled extensive in vitro biological characterisation of the chemotatic stimuli (factors) and the cellular events of migration. The chemotatic stimuli include products of complement activation, fibrinolytic and kinin generating systems, collagen products as well as products of bacterial growth and products released from virus-infected tissues. Chemotatic factors are also released as a result of lymphocyte activation and phagocytosis by neutrophils. Other neutrophils products released during phagocytosis activate the complement system. A complex mechanism for limiting production or activity of chemotactic factors has been identified. These antichemotatic agents include serum and cell-derived chemotactic factor inactivators as well as specific inhibitors of leucocyte migration and complement inactivators released from neutrophils during the phagocytic process. The mechanism by which cells respond to chemotatic factors is poorly understood by cell adherence to the substratum, cell deformability, random migration, and directed migration are required. These processes are complex and require modifications of the leucocyte surface, calcium and magnesium, activation of esterases, function of contractile elements and assembly of a cytoskeleton, which is probably modulated by cyclic nucleotide metabolism.