多核白血球遊走能にかんする研究 : 腎孟腎炎患者および膀胱腫瘍患者について

Abstract

It is becoming increasingly apparent that many microorganisms that are not ordinarily considered pathogenic or virulent may, under certain circumstances, become so when the immunologic capacity of the host is impaired. These infections are referred to as opportunistic infections (e.g., Pseudomonas aeruginosa or Serratia marcescens) and are assuming increasing clinical importance in the urological field as the number of patients with compromised defense mechanisms. Host defenses against bacterial infections are at once local and systemic, non-specific and specific, however non-specific defense mechanism firstly react to bacterial infection. After bacterial infection occur, microorganisms may be engulfed by wandering tissue macrophages and polymorphonuclear (PNM) leukocytes or monocytes emigrated from capillary vessels at the site of inflammatory change. These cellular elements, especially PMN leukocytes, are phagocytes of invaded microorganisms. Accumulation of PMN leukocytes in local tissue sites infected with microorganisms is an important event in the host defense from the point of view above these facts. PMN leukocyte chemotaxis is an important stage for the first step of PMN leukocyte function as phagocytosis. I studied PMN leukocyte chemotaxis with 20 patients having pyelonephritis or bladder tumor using an agarose plate technique, and furthermore studied the effect of five different antibiotics on chemotaxis of PMN leukocytes with the patients of pyelonephritis. Quantitation of chemotaxis was done by measuring in centimeters the linear distance the cells have migrated from the margin of the well toward the bacterial chemotatic factor. Random mobility was represented by the distance the cells have migrated from the well margin toward the control medium. Linear distances of PMN leukocyte migration was done under microscopic measurement (X 40). The results were summarized in the followings. [A] Group of pyelonephritis. 1) Leukocytes from 20 patients and 30 healthy subjects (control) were examined. In all patients, the value of PMN leukocyte chemotaxis was higher than in the controls. The mean value of PMN leukocyte chemotaxis in patients was 5.2±0.2 cm, and the mean value in the controls was 3.3±0.1 cm; this difference was statistically significant (p<0.001). The mean value of random mobility in 20 patients was 3.1 ±0.2 cm, and the mean value in the controls was 1.5 ±0.1cm. Random mobility also was enhanced in 20 patients compared with normal subjects; this difference was found to be statistically significant (p<0.001). This result demonstrated an enhancement in the chemotactic response of leukocytes derived from patients. It has been shown experimentally that increases in the intra-leukocytic level of cyclic GMP enhance chemotaxis, while increases in the level of cyclic AMP inhibit chemotaxis. It seems logical to assume that a decreased cyclic AMP/cyclic GMP ratio, similar to the imbalance between these 2 cyclic nucleotides found in the patients, might also be present in leukocytes derived from patients with pyelonephritis. 2) The results of the effect of five different antibiotics on PMN leukocyte chemotaxis with the patients of pyelonephritis were summarized in the followings; (a) There was no effect of beta-lactam antibiotics (CBPC, CER) on the chemotaxis. (b) Tetracycline of the therapeutic blood level (3.12µg/ml) appeared to inhibit PMN leukocyte chemotaxis, and the peak of inhibition showed at the concentration of 100µg/ml. Although, there was a tendency to fail to suppress PMN leukocyte chemotaxis in the concentration of 500µg/ml. The low levels of tetracycline may effect the microfilaments of leukocytes, whereas the increased production of lactic acid by leukocytes in the presence of 500µg/ml of tetracycline may be a manifestation of metabolic effect of the drug. (c) Chloramphenicol in concentrations of 25µg/ml, 100µg/ml and 500µg/ml inhibited the PMN leukocyte chemotaxis, and the peak of inhibition was shown at the concentration of 500µg/ml. In the presence of chloramphenicol, the increased production of intracellular cyclic AMP in leukocytes restrict an intact system of cytoplasmic microtubules. [B] Group of bladder tumors. 1) Twenty patients with transitional cell carcinoma of the bladder were studied. In all patients, the mean value of PMN leukocyte chemotaxis was 3.1 ±0.3 cm. This value was almost the same in the controls, and there was no statistical difference. However, the mean value of PMN leukocyte chemotaxis was 3.0±0.2 cm in the 14 patients without infection, and the mean value in the controls was 3.3±0.1cm; this difference was statistically significant (p<0.05). The results demonstrated a depression in the chemotactic response of PMN leukocytes derived from patients with bladder tumor. The mechanism for depression of in vitro chemotactic responsiveness of PMN leukocytes from tumorbearing individuals is not known. It is postulated by experiments in vitro that the chemotactic inhibitors by tumor cells is effectual at retarding the migration of polymorphonuclear leukocytes. 2) The mean value of PMN leukocyte chemotaxis in 7 patients under chemotherapy was almost the same value in 13 patients under no-chemotherapy. However, many chemotherapeutic agents produce neutropenia and impairement of the ability to stimulate hexose-monophosphate shunt activity in PMN leukocytes which is an established alteration of host defense which prediposes patients to infections. It is postulated that patients who are treated with various chemotherapeutic agents either singly or in combination may be at an increased risk of infection due to functional impairement of their PMN leukocytes even when their peripheral blood and bone marrow cells exhibit normal morphology.