Spontaneous production of eosinophil chemotactic factors by T lymphocytes from patients with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia.

Publisher Summary This chapter discusses the separation, characterization, and functional specificity of a number of chemotactic factors, which may satisfy many criteria making them acceptable as inflammatory leukocyte chemotactic factors. They are separated from the sites of inflammatory lesions resulting from immune responses as experimental models. The chapter focuses on three neutrophil chemotactic factors, three macrophage chemotactic factors (MCF-a, b, and c), four lymphocyte chemotactic factors (LCF-a, b, c, and d), and three eosinophil chemotactic factors. It is of special importance that highly purified chemotactic factors among them exhibited cell-type–specific functions for the associated leukocytes in vitro, as well as in vivo. The intradermal injection of these purified chemotactic factors clearly provoked adherence of the associated leukocytes to the vascular endothelium of the venules, followed by selective emigration of the cells into the perivascular locations. Cinemicrophotographic and ultrastructural observations on neutrophil emigration induced by leukoegresin have given one direction to the analysis of morphological sequence in the emigration of other leukocytes in vivo.

Chemotactic factors associated with leukocyte emigration in immune tissue injury: their separation, characterization, and functional specificity.

The granuloma of patients with Kimura's disease characterized by tissue and peripheral blood eosinophilia was reviewed with respect to eosinophil infiltration. An infiltrate of inflammatory cells with histiocytes and a sprinkling of eosinophils were observed in the fibrous stroma surrounding the newly formed vessels. Mast cells were rarely seen in the areas where eosinophils were grouped together. Three different eosinophil chemotactic factors (ECF) were isolated from the granulomas of Kimura's disease. They were termed as low molecular weight (LMW), intermediate molecular weight (IMW), and high molecular weight (HMW)-ECF according to the profile on gel filtration (LMW-ECF, about 500; IMW-ECF, about 12,500; HMW-ECF, 45,000-70,000). In terms of their activity when extracted from the granuloma, LMW-ECF and HMW-ECF seemed to be major natural mediators for the tissue eosinophilia, whereas IMW-ECF was a minor one. In an in vitro system, it was shown that granuloma lymphoid cells produce spontaneously at least two ECF having similar properties to LMW- and HMW-ECF, respectively. By analysis with monoclonal antibodies, granuloma T cells, probably OKT4-positive cells, were shown to be responsible for the production of those two ECF. It was thus suggested that prolonged synthesis of LMW- and HMW-ECF by OKT4-positive T cells plays a crucial role in the local eosinophilia of Kimura's disease.

Eosinophil chemotactic factors from granuloma of Kimura's disease, with special reference to T lymphocyte-derived factors.

Peripheral OKT4-positive T lymphocytes from patients with hypereosinophilia spontaneously and selectively produced an eosinophil chemotactic factor (ECF) with chemokinetic activity. The molecular weight of the ECF was about 45,000 to 70,000. A possible mechanism of its spontaneous production by T lymphocytes was analyzed. Culture supernatants of blood monocytes from the patients showed little or no ECF activity, but they had a potency to induce the ECF production from T lymphocytes from normal donors when the cells were stimulated by the supernatants, which suggests that a monocyte-derived soluble factor (MDF) stimulated T lymphocytes to produce an ECF resembling this spontaneously produced ECF from the patients. MDF seemed to be a synthesized protein by the cells. Gel filtration indicated that molecular weight of MDF ranged between 70,000 and 100,000. MDF activity was stable at 56 degrees C for 30 min but more, supernatants of stimulated monocytes by lipopolysaccharide or silica particles failed to show ECF-producing activity, whereas they showed evident lymphocyte-activation activity. Neither recombinant IL-1 nor IL-2 had ECF and ECF-producing activity. From the present experiments, it was suggested that MDF was at least partly involved in the induction of ECF production by OKT4-positive T lymphocytes in patients with hypereosinophilia.

Production of an eosinophil chemotactic lymphokine by a monocyte-derived factor from patients with hypereosinophilia.

Our particular attention in this article was given to natural mediators for macrophages isolated from the sites of tissue injury. A number of chemotactic factors, which may satisfy many criteria making them acceptable as inflammatory leucocyte chemotactic factors, has been separated. Among them, our laboratory has isolated three macrophage (monocyte) chemotactic factors (MCF-a, -b and -c). Their purification, characterization and functional specificity are discussed.

Chemotaxis of macrophage in inflammation.

In complement-depleted condition induced by cobra venom factor (CoF), tissue macrophage reaction and macrophage chemotactic activity (MCA) in skin extract from skin lesions induced by DNP-Ascaris extract (DNP-As) were decreased, respectively. MCA in the fraction containing macrophage chemotactic factor b (B fraction) was decreased completely. While MCA in the fraction containing macrophage chemotactic factor a and c (A fraction) was affected only slightly. These results suggested that the decrease of MCA of Infraction might be associated with depletion of complement system by CoF. Using anti-C5 antibody, it was confirmed that macrophage chemotactic factor-b (MCF-b) (MW 14,000: thermostable) might be derived from C5 fragment in vivo.

Yasunobu Hirotsu

Papers

A C5-Derived Macrophage Chemotactic Factor from DNP-Ascaris Extract-Induced Skin Lesion in Guinea Pigs