Studies on Neutrophil Function I. Physiological and Pharmacological Aspects

Abstract

During inflammation, the circulating neutrophil adheres to the altered venular endothelium (Marchesi, 1964; Cotran, 1965), and emigrates between the endothelial cells into the tissue towards its prey. Both phenomena were first observed by Dutrochet in 1824 in the small blood vessels of the tail of the frog tadpole. Accurate observations on the margination and emigration of leucocytes in inflammation were made between 1833 and 1850 by Wagner, Waller, Addison and Wharton–Jones, and later by Cohnheim and Adami. The history of the early work is reviewed by Grant (1965). The amoeboid locomotion of leucocytes was studied by Metchnikoff at the end of the 19th century. He introduced the term phagocytosis and was the first to recognize it as a defence reaction (1893), his contemporaries including Klebs, Koch, Waldeyer and Virchow having regarded leucocytes as a source of dissemination of the bacteria they had observed within them. Pseudopodia form and enclose the particles to be phagocytosed within a phagocytic vacuole into which are discharged the enzyme‐rich contents of the neutrophil granules (Senda, 1962; Zucker‐Franklin and Hirsch, 1964; Zatti, Rossi and Meneghell, 1965). This process requires the participation of intrinsic neutrophil mechanisms and of extrinsic serum and tissue components. The biochemical aspects of neutrophil function at rest and in action have been investigated, (Karnovsky, 1962; Rossi and Zatti, 1964; Ohta, 1964a, b; Perry, 1964; Zatti et al., 1965) but recently more attention has been directed towards the extracellular components concerned in leucocyte emigration (Hurley, 1964), adhesiveness (Rabinowitz, 1964), chemotaxis (Boyden, North and Faulkner, 1965; Ward, Cochrane and Müller‐Eberhard, 1965), phagocytosis (Tullis and Surgenor, 1950; Nelson and Lebrun, 1956; Boyden, 1963; Gerlings‐Petersen and Pondman, 1964; Vaughan, 1965), and the post‐phagocytic phase (Li, Mudd and Kapral, 1963; Archer, 1964; Boyden et al., 1965). In the present study, adhesiveness and phagocytosis were the two aspects of neutrophil function assessed in vitro under physiological and pharmacological conditions (I) and in pathological states (II), in the hope of casting light on the causes of disturbed function in a variety of pathological states.

Motility and Adhesiveness in Human Neutrophils

“…(a) Adhesiveness to serum-treated glass was affected by Mg++ levels in the medium; a finding consistent with the reports of others (4,(20)(21)(22)(23) (26). With one exception, deactivated neutrophils were able to change shape in response to a second chemotactic stimulus.…”

“…Albumin decreases neutrophil adherence to glass. (b) Deficiency of Mg++ in the culture medium significantly reduces PMN migration in the Boyden assay (13,33) and adhesiveness to protein-coated glass (4,(20)(21)(22)(23) (35). This effect is apparently a result of casein bound to the filter.…”

Reduction of Phagocyte Adherence by Nephritic Sera: Relation to Complement Activation

“…A number of investigators have shown complement to be necessary for normal PAg when phagocytes are incubated with serum. Treatment of NHS by chelation of divalent cations (3,4,9,13,17,25) or heating (3,13,17,25) results in decreased adherence. In addition, magnesium has been shown to preferentially restore adherence of cells incubated in chelated serum (4,10,13).…”

“…Phagocyte adherence has been studied using a variety of in \xifro techniques which substitute negatively changed surfaces for vascular endothelium (25). Adherence of phagocytes to vascular endothelium has been shown to be prerequisite for many normal functions including diapedesis (I), response to chemotactic stimuli (3), and, in most instances, phagocytosis (39).…”

Phagocytic activity and hyperpolarizing responses in L‐strain mouse fibroblasts.

“…consistently inhibited the uptake of beads by L cells ( Okamura, Ishibashi & Takano, 1979). On the other hand, no significant inhibition was observed with the application of colchicine or vinblastine (Table 2), as in macrophages (Pesanti & Axline, 1975;Takayama et al 1975;Munthe-Kaas, 1976) and in leukocytes (Penny, Galton, Scott & Eisen, 1966;Malawista & Bodel, 1967 Fig. 5.…”