An antigen expressed by cells of the myelo-monocytic lineage.

We describe an antigen(s) characterized by a heteroantiserum raised in rabbits against mature human granulocytes. This antigen was found on neutrophils, monocytes, platelets, acute and chronic myelocytic leukemia cells and on granulocyte-macrophage progenitor cells grown in agar. It was not found on lymphocytes, eosinophils, erythrocytes, or erythroid progenitor cells. On the basis of tissue distribution and absorption studies, the antigen (tentatively designated the "myelo-monocytic" antigen) is distinct from antigens previously identified on human neutrophils. Restriction of the "myelo-monocytic" antigen to normal and malignant cells of the myelo-monocytic series suggests that it may represent a normal differentiation antigen of the myelo-monocytic lineage.

Levamisole-associated neutropenia and autoimmune granulocytotoxins.

To investigate possible immune mechanisms responsible for levamisole-associated neutropenia we tested patients with bladder cancer on levamisole therapy. Autoimmune and complement-dependent granulocytotoxic antibodies were detected in 3 patients with levamisole-induced neutropenia. The granulocytopenia appeared to be causally related to the presence of autoantibodies in that pretreatment serum or serum obtained after the restoration of neutrophil counts showed diminished or no granulocytotoxic reactivity. In addition, granulocytotoxins were found in 6 out of 20 (30%) patients receiving levamisole compared to only 2 out of 28 (7.1%) patients on no levamisole or placebo (P less than 0.06). Hence, screening for granulocytotoxins may forewarn of neutropenia in patients receiving levamisole for a variety of clinical diseases.

Immunological surveillance against neoplasia: an immunological quandary.

Immunological endeavor in recent years calls for a reappraisal of the concept of immunosurveillance against neoplasia. This concept proposes an immunological policing system capable of aborting tumor growth by the recognition of "nonself" tumor associated antigens on neoplastic cells. The model is supported by evidence of tumor induction in the immunosuppressed host and the demonstration of an immune response to tumors in animals. The occurrence of tumor, regarded as a failure of immunosurveillance, is attributed to selection of neoplastic cells for immunological or other reasons or abnormal humoral or cellular antitumor immune responses. However protagonists of the postulate are faced with mounting evidence that fails to support the surveillance hypothesis. These observations include, inter alia, the monoclonality of certain tumors, the low incidence of spontaneous tumors in genetically immunodeficient mice and immunological privileged sites, and new ideas about the pathogenesis of lymphoproliferative neoplasms. However, contradictory arguments are not sufficiently substantiated to prosecute the case against surveillance conclusively. In citing highlights of the evolving quandary, both the pros and cons of immunological surveillance are presented here.

Autoimmune cytotoxic granulocyte antibodies in normal persons and various diseases.

Of 400 female and 58 normal nonommunized male sera approximately 10% were cytotoxic for a panel of allogeneic granulocytes. Sera with strong alloreactivity were also autoreactive, which emphasized the large autoimmune component of most alloantisera against granulocytes. The cytotoxic granulocyte autoantibodies were complement dependent, of the IgM class, and exhibited optimum cytotoxic activity in vitro at 5 degrees C precomplement incubation temperatures with papain-treated cells. The sera were unreactive with autologous or allogeneic B and T lymphocytes, monocytes, and red blood cells but were cytotoxic for adult and cord granulocytes, eosinophils, and chronic myeloid leukemia cells. Granulocyte autoantibodies were present in 53% of sera from 57 patients with systemic lupus erythematosus (p less than 0.00002) but were not found in increased frequency in the sera of patients with 28 other diseases. We conclude that a single tissue-specific antigenic determinant(s) called "G" may be present on granulocytes and is the target of naturally occurring autoantibodies.

Cell surface antigens detected on mature and leukemic granulocytic populations by cytotoxicity testing.

Using a microcytotoxicity assay, the serological reactivity of human granulocytes, namely neutrophils and eosinophils, and chronic myeloid leukemia (CML) cells and cultured CML cell lines (K562, NALM-1) were examined. Mature granulocyte forms and cord granulocytes are readily lysed by specific granulocyte cytotoxins that do not react with random T and B lymphocytes, monocytes, red blood cells, or platelets. Furthermore, certain antisera were preferentially cytotoxic for eosinophil-enriched populations. Granulocytotoxin detected antigens on one of three CML blast cell populations tested and K562, but failed to react with NALM-1. By cytotoxicity, mature granulocytes were poor targets for B2-microglobulin and the appropriate HLA antisera although both sera types are absorbed with granulocytes. Furthermore, granulocytes did not possess B-lymphocytes (Ia-like) or blood group A, B, and Rh (D) antigens. Except for K562, both HLA and heterologous B-lymphocyte antisera were cytotoxic for the CML blast cell populations tested.

First 24 hours of acute pancreatitis. A biochemical and endocrine evaluation of initial versus repeated attacks.

Differences in metabolic homeostasis in 12 patients with initial vs. eight patients with repeated attacks of acute pancreatitis have been compared during the acute phase of the disease. As a group, subjects with a previous history of pancreatitis had significantly lower glucagon concentrations (P less than 0.002) for the over all 24-hour study period. Conversely, the serum concentrations of blood sugar, insulin, growth hormone, gastrin, cortisol, nonesterified fatty acids, triglycerides and cholesterol failed to distinguish between the two patient groups. Likewise, immunoreactive plasma parathyroid hormone and calcitonin levels were comparable in both patient populations. Of the measurements considered, it would appear therefore that plasma immunoreactive glucagon is the best indicator of previous pancreatic inflammation. Evaluation of parenchymal integrity during an episode of acute pancreatitis would be of prognostic and therapeutic value in this disease.

Serological characterization of human monocytes for HLA, B-lymphocyte, granulocyte, and monocyte-associated antigens by cytotoxicity testing.

Highly enriched preparations of monocytes, B and T lymphocytes, and granulocytes from 18 normal donors were serotyped in parallel in a complement-dependent cytotoxicity assay using allogeneic and heterologous antisera defining three independent tissue antigen systems. HLA and B-lymphocyte tissue antigens were detected on human monocytes although granulocyte antigens were absent. By cytotoxicity testing the presence of Ia-like antigens on monocytes was significantly diminished compared to the autologous B-lymphocyte population and has important implications in B-lymphocyte serology. The study indentified a number of human antisera obtained from multitransfused subjects and pre- and post-transplant organ recipients that were non-HLA and appeared to define monocyte-associated antigens. The serological implications of surface antigen expression on human monocytes compared with other peripheral blood cells are discussed.

Human granulocyte antigens detected on leukemia cells and a chronic myelogenous cell line.

Normal human granulocyte alloantigens were found on chronic myelogenous, acute myeloblastic leukemia cells, and a cell line of chronic myeloblastic origin (K562). Antigens were detected by human antisera positive for normal peripheral blood granulocytes but devoid of HLA activity. Very few acute lymphoblastic leukemia cells reacted positively, and none of the chronic lymphocytic leukemia cells seemed to bear granulocyte surface antigens. The recognition of these normal tissue isoantigens on myeloblastic leukemia cells is a necessary prerequisite for the identification of "leukemia-specific" of "leukemia-associated" antigens.

Autoimmune cytotoxic granulocyte antibodies in health and disease.

Optimum serologic reactivity is observed if papain-treated granulocytes are reacted with cytotoxic antibody at low (5 degrees C) rather than warm (22 degrees C) precomplement incubation temperatures. Favorable in vitro conditions have allowed the identification of cytotoxic granulocyte antibodies in approximately 12% of nonimmunized normal males and females. Furthermore, the incidence of granulocytotoxic antisera in a group of alloimmunized patients did not exceed that observed in the normal population. In two cases cited, a normal male and a patient with pathologic neutropenia, cytotoxic antibodies against allogeneic granulocytes were autoreactive against the autologous cells of the serum producer. In the latter subject, an inverse association was demonstrated between the presence of autoantibody and the circulating neutrophil count. The incidence of granulocytotoxins in various diseases has been given and appears raised in systemic lupus erythematosus and asthma.

Group-specific human granulocyte antigens on a chronic myelogenous leukemia cell line with a Philadelphia chromosome marker.

Group-specific human granulocyte antigens are serologically detectable with granulocytotoxic-positive human alloantisera on a cell line, K562, of chronic myelogenous leukemia origin which bears a Philadelphia chromosomal marker. The same cell line lacks serologically detectable HLA, B2 microglobulin, and B-lymphocyte antigens. Granulocyte antigens are important cell markers for cell lines of suspected myeloid lineage.

The effect of carbachol on the gallbladder in Black and White subjects.

The effect of carbachol on the gallbladder was assessed in 24 White and 24 Black volunteers. The results suggest that in Blacks the gallbladder empties to a signigicantly greater degree than it does in Whites after administration of carbachol. This fact may account, in part, for the lower incidence of cholelithiasis in Black populations. No difference in gallbladder contractility was found between men and women nor did gallbladder response appear to be influence by hormonal factors.

Antigenic specificities detected on papainized human granulocytes by microgranulocytotoxicity.

A reliable and routine identification of human granulocyte antigens is possible with an improved microgranulocytotoxicity assay. Freshly isolated, papainized granulocytes, an extended incubation period, and alcohol to prevent the adherence of cells are important factors enhancing cellular reactivity. Absorption studies indicate an absence of B-lymphocyte alloantigens on granulocytes. Five tentative granulocyte specificities were defined with granulocytotoxic non-HLA alloantisera. Sib-pair studies suggest the independent chromosomal segregation of the granulocyte and HLA antigen systems.

Two-step separation of human peripheral blood monocytes on discontinuous density gradients of colloidal silica-polyvinylpyrrolidinone.

Normal human peripheral blood monocytes were purified by a two-step separation. The first step, the standard Ficoll--Hypaque (F--H) buoyant density centrifugation, yielded mainly mononuclear cells, of which 24 +/- 9% were monocytes. Isopycnic centrifugation on discontinuous gradients of colloidal silica polyvinylpyrrolidinone (CS-PVP) further separated these mononuclear cells. The density interface between 1.070 and 1.060 g/ml yielded 82 +/- 7% monocytes, 5 +/- 4% granulocytes and 13 +/- 8% lymphocytes. Sixty-six percent of the monocytes obtained after F--H separation were recovered in this layer. The monocytes were intact and viable and retained their ability to phagocytose and kill Candida pseudotropicalis and to spread on glass coverslips. Motility (both random and towards a chemoattractant) was retained but was quantitatively less than after F--H separation alone. The relative purity of the monocyte population allowed assessment of major histocompatibility surface antigens by serotyping. This confirmed the presence of HLA and Ia-like antigens on monocytes.