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Leukocyte (white blood cell) adhesion deficiency (LAD) is an inherited disease in which molecules on the surface of leukocytes, known as the leukocyte adhesion molecules, are defective. The leukocyte adhesion molecules include lymphocyte function-associated Ag-1 (CD11a/CD18), CR3 (CD11b/CD18) and p150,95 (CD11c/CD18). The immune system of patients with LAD is impaired and results in varied clinical manifestations, with a predominance of bacterial infections. Defects are seen in the various types of leukocytes including granulocytes, monocytes and lymphocytes. Studies in tissue culture show that cellular uptake or phagocytosis (such as ingestion and digestion of bacteria) is impaired due to defective CR3 molecules, which are normally involved in phagocytosis. Phagocytosis can also be mediated through another molecule, the FcR receptor. There are three classes of FcR receptors found on the various types of leukocytes: FcRI, FcRII, and FcRIII. The expression of the various classes and functions of the receptors on granulocytes and monocytes were examined in patients with LAD. Increased binding and uptake were observed in granulocytes, but not in monocytes. Additional studies revealed that the class of FcR receptors that is expressed to a greater extent in patients with LAD is FcRI, and not FcRII or FcRIII. In normal conditions, FcRI is expressed on monocytes, but has also been shown to be expressed on granulocytes activated by a certain cytokine (cellular factor), interferon-gamma. However, it is thought that interferon-gamma is not involved in the activation of FcRI in patients with LAD. The mechanism for activation of FcRI on granulocytes in patients with LAD is not understood. (Consumer Summary produced by Reliance Medical Information, Inc.)

To directly measure some of the chemical events that occur during an allergic skin reaction, researchers have devised a clever method in which a chamber is placed over a small area of denuded dermis. Previous studies using this method have shown that a large number of neutrophils, a type of white blood cell, accumulate during an allergic reaction. To determine if these neutrophils are contributing pathogenic chemicals to the reaction site, the accumulation of several different substances was measured. Lactoferrin, elastase, and myeloperoxidase, all present in granules, were measured, as was lactic dehydrogenase, which is present in cell cytoplasm. The amount of histamine was also evaluated; this substance is present in mast cells and basophils, and other cells involved in the allergic reaction. (Histamine is not present in neutrophils.) Results obtained from 13 volunteers with allergies to pollen revealed that lactoferrin and elastase accumulated slowly over a period of four hours after the allergic stimulus. It was found that the levels of elastase and lactoferrin did not reflect the accumulation of neutrophils during this period. However, lactoferrin levels correlated with the amount of histamine released during the first hour of the reaction. This finding indicates that, during an allergic reaction, neutrophil components are released in living tissue. The relation of lactoferrin to the release of histamine, which is mediated by cells other than neutrophils, suggests that the release of lactoferrin may be related to the earlier activation of the mast cells. Since lactoferrin plays a role in reactive oxidants effects, and elastase is a nonspecific enzyme which degrades proteins, it seems likely that these substances may play a role in the tissue damage which occurs in the later phases of allergic responses. (Consumer Summary produced by Reliance Medical Information, Inc.)

While allergic reactions are generally associated with allergen-specific immunoglobulin E (IgE), there is some evidence that a subset of immunoglobulin subclass 4 (IgG4) molecules may be involved in allergic processes. (Basophils are a type of white blood cell that plays an important role in the allergic response.) Although the presence of IgG4 molecules on basophils has not been established, the stimulation of basophils with antibodies against IgG4 results in the release of enzyme-containing granules and histamine. Since the release of these granules is both easily visible and readily quantifiable, degranulation was used as the basis of a more detailed examination of the role of IgG4 in the allergic response. Although the net result was the same, it was found that basophils can be affected by antibodies to IgG4 in two distinct ways. At higher antibody concentrations, ranging from 10 to 100 micrograms per milliliter, anti-IgG4 could affect the basophils directly and induce the release of the granules without the presence of any other cell. However, at over a thousand-fold lower concentrations, ranging from 1 to 100 picograms per milliliter, anti-IgG4 could induce degranulation of the basophils when eosinophils were present. Eosinophils, a subclass of white blood cells referred to as polymorphonuclear cells, apparently respond to anti-IgG4 and release substances which then induce the granulation of the basophil. Experiments with the tissue culture supernatant of IgG4-treated eosinophils revealed the presence of a positively charged protein, capable of inducing the release of granules by the basophils. There are, therefore, at least two distinct mechanisms by which the degranulation of basophils results from a pathway involving IgG4. (Consumer Summary produced by Reliance Medical Information, Inc.)

Granulocyte macrophage colony stimulating factor (GM-CSF) causes the proliferation and maturation of granulocyte and macrophage blood cells. Human GM-CSF can be produced by biotechnological methods in large quantities. Recombinant GM-CSF caused the activation of neutrophils when it was given to human neutrophils in culture. There was an increase in protein synthesis in general and an increase of at least 10 identifiable proteins, including two proteins that are cationic (have a basic pH). Neutrophils can kill microorganisms, such as bacteria, fungi, and parasites, by two major pathways: one, with oxygen metabolites and the other without oxygen. The latter includes cationic proteins. The cationic proteins produced by GM-CSF-stimulated neutrophils were cultured with the bacteria Salmonella typhimurium, which can cause food poisoning, and caused death of the bacteria. Therefore, GM-CSF can enhance the ability of neutrophils to kill bacteria by cationic proteins. (Consumer Summary produced by Reliance Medical Information, Inc.)