Leukocyte Physiology Research Articles

Leukocyte adhesion--a fundamental process in leukocyte physiology.

Leukocyte adhesion is of pivotal functional importance. The adhesion involves several different adhesion molecules, the most important of which are the leukocyte beta 2-integrins (CD11/CD18), the intercellular adhesion molecules, and the selectins. We and others have extensively studied the specificity and binding sites in the integrins and the intercellular adhesion molecules for their receptors and ligands. The integrins have to become activated to exert their functions but the possible mechanisms of activation remain poorly understood. Importantly, a few novel intercellular adhesion molecules have been recently described, which seem to function only in specific tissues. Furthermore, it is becoming increasingly apparent that changes in integrins and intercellular adhesion molecules are associated with a number of acute and chronic diseases.

Potassium channels in leukocytes and toxins that block them Structure, function and therapeutic implications

Yet to appear in immunology text books, potassium channels are an important class of signaling molecules that play crucial roles in the physiology of leukocytes. By maintaining membrane potential, modulating calcium signaling or regulating cell volume, they tightly control leukocyte development and activation. The discovery of peptide toxins that selectively and potently block potassium channels has unraveled the functional relevance of these membrane proteins in leukocyte signaling. In addition, these toxins have served as powerful tools in high-throughput screening and as molecular probes to study channel structure. This review summarizes the expression pattern, molecular determinants, physiological roles and therapeutic significance of potassium channels in white blood cells and the peptide toxins that block them.

Structure and function of CD45: a leukocyte-specific protein tyrosine phosphatase.

CD45 is a large abundant leukocyte-specific cell surface glycoprotein 1. It is structurally heterogeneous consisting of a family of isoforms (Mr ~ 180-220K) that are distributed in characteristic cell-type specific patterns on different leukocyte sUbpopulations. Because of its leukocyte-specific tissue distribution, CD45 is a useful marker for the differential diagnosis of undifferentiated lymphoma 2. The primary structures of rat, mouse and human CD45 deduced from cDNA sequencing in the mid-1980’s revealed that the cytoplasmic domain of CD45 was unusually large 1, confirming earlier studies of a mutant CD45 molecule 3. Charbonneau et al. showed in 1988 that two tandem imperfect repeats within the large cytoplasmic domain of CD45 had highly significant sequence similarity with PTP1B, a soluble ~37K human placental protein tyrosine phosphatase (PTP) 4. Subsequently, CD45 was shown to have intrinsic PTP activity 5, suggesting that transmembrane PTPs might represent a novel class of receptors that oppose the action of protein tyrosine kinases (PTKs) and playa fundamental role in the regulation of cell growth and differentiation. Other putative transmembrane and intracellular PTPs in organisms as diverse as higher eukaryotes, Drosophila, yeast, bacteria, and viruses have now been identified and the complete primary structures of at least twenty PTPs have been determined (reviewed in Ref 6). CD45 is the best characterized of the transmembrane PTPs and serves as a prototype for this class of enzyme. An understanding of the function of CD45 in leukocyte physiology requires identification of its substrates, elucidation of the structuralfeatures of the molecule essential for PTP activity, and information about how its activity is regulated. This paper will review recent progress in defining the role of CD45 in lymphocyte signal transduction and summarize the current status of the rapidly growing PTP family.

The pivotal role of the Leu-CAM and ICAM molecules in human leukocyte adhesion

Cellular adhesion is of fundamental importance in leukocyte physiology. It is a complex, strictly regulated process, which involves the participation of several cell surface glycoproteins. Among the most important are the Leu-CAMs or the DC11 / CD18 integrin receptors, and their adhesion ligands ICAM-1 (CD54) and ICAM-2. In this review we summarize some recent work on various aspects of these molecules.

Glycosaminoglycan changes involved in polymorphonuclear leukocyte activation in vitro.

The changes of cell coat and endocellular glycosaminoglycans associated with adhesion of polymorphonuclear leukocytes to tissue culture dishes were studied by electrophoresis on cellulose acetate. Polymorphonuclear leukocytes are coated by chondroitin 4 sulphate, while undersulphated chondroitin 4 sulphate and heparan sulphate are present in the cytoplasm. Upon adhesion polymorphonuclear leukocytes shed into the culture medium chondroitin 4 sulphate and concomitantly hyaluronic acid and heparan sulphate are exposed at the cell surface and shed into the culture medium. The role of these compounds in polymorphonuclear leukocyte physiology is discussed.

The White Cell

This discussion of the white blood cell is aimed at a sophisticated audience, and, while it cuts across many disciplines of cell biology, microbiology, immunology, viral oncology, and cell and tissue kinetics, it would be of interest primarily to the hematologist. The objectives of this book, as stated in the preface, are to review critically the existing body of knowledge of normal and abnormal leukocyte physiology and, in doing so, to reach a compromise between a superficial treatment and a set of encyclopedias. The result of this effort is a large book, both literally and figuratively. The book has been divided into three parts, each devoted to a major class of white blood cell. Each part has a similar construction, in which the reader is led from a presentation of basic information about morphogenesis, production, composition, and metabolism, into a discussion of abnormalities of these various aspects of leukocyte physiology.

Physiology of the Granulocyte—Part 1

The determination of the white blood cell count and differential count is important in the medical examination of a patient yet the basic mechanisms guiding leukocyte turnover and dynamics remain largely undefined. This is more than an academic problem since a better understanding of the life of the leukocyte is important in the treatment of leukemia and in the achievement of selective toxicity to the neoplastic cell in the therapy of patients with cancer. The height of the white blood cell count is affected by numerous factors and once leukocytes leave the vascular tree there is no simple way of determining their ultimate fate. However, in spite of many technical problems, sound data have been accumulated concerning leukocyte production, release from the bone marrow, intravascular life span, and distribution. In this paper, the significant information dealing with leukocyte physiology is reviewed with particular emphasis on the granulocyte.

The Physiology and Pathology of Leukocytes

The Physiology and Pathology of Leukocytes

The Physiology and Pathology of Leukocytes.

The Physiology and Pathology of Leukocytes.

The dynamics of leukopenia and leukocytosis.

Excerpt Many features of the physiology of leukocytes are controversial. The origin of certain cells—for example, the monocyte and the plasma cell—is disputed. The functions of many of the cell spe...

Newer concepts in leukocyte physiology and their clinical significance.

It is inherent in most fields of investigation that problems which can be expressed in quantitative terms are the most actively pursued. Quantitation permits planned controlled experimentation susceptible to logical reasoning, with eventual understanding. In hematology, techniques for quantitation of normal and abnormal erythropoiesis have been developed, and knowledge concerning red cell disorders has increased concurrently. Similar techniques for the study of leukopoiesis and leukocyte life span and distribution in normal and abnormal states have only begun to be developed. Part of the difficulty in expressing leukocyte physiology in the same quantitative terms as for the red cell lies in the fact the leukocyte is not confined to the intravascular circulation. Labelled red cells can be followed until their death by sampling the peripheral blood at intervals. The leukocyte, on the other hand, is more difficult to label and, if transferred into a recipient, disappears from the circulation almost immediately.

The leukocytes and the leukopathies.

Early investigations of the leukocytes and the leukopathies centered largely around numerical and morphological variations in the peripheral blood. Later, the widespread use of marrow aspiration and lymph node bi­ opsy called attention to the value of these procedures in understanding and diagnosing the leukopathies. Still more recently efforts have been made to investigate the intracellular biochemical and enzymatic machinery present in the leukocytes and its derangement in disease. The physiology of leukocytes in health and disease has been the subject of widespread investigation relat­ ing to leukocyte life span, mechanisms of removal, phagocytosis, and other physiologic functions. Despite the large number of studies bearing on these and related problems, it must be admitted that large gaps in knowledge exist where, in reality, very little is known about the actual functions, activities, and destiny of the leukocytes. It is the purpose of this review to evaluate the literature bearing on the leukocyte and leukopathic disorders since approxi­ mately January of 1953.