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Biomedical subjects

R Rocklin

Publications and source records attributed to R Rocklin.

14 recordsLinked to original sources
PubMed1992

Physiological studies with human leukocyte inhibitory factor.

LIF has been shown to be a potentially important activator of neutrophil function. By means of its dose-dependent dichotomous effects on chemotaxis, LIF can be predicted to both enhance the potency of chemotactic stimuli and promote the passive accumulation of PMN at inflammatory loci. Furthermore, LIF's stimulatory effects on both PMN- and endothelial cell-mediated adherence will promote the migration of neutrophils from the circulation to the inflammatory site. We have demonstrated LIF stimulation of fMLP, CR1, and CR3 expression and function, as well a stimulated Fc gamma RIII function. Through both receptor-dependent and -independent effects. LIF produces increased target cell attachment, phagocytosis, respiratory burst activity, and degranulation. Together, these effects result in a significant increase in killing of both phagocytosed targets and extracellular targets.

Chemotaxis, Leukocyte↗
PubMed1990

Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects.

The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl-alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha-tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products.

Aged↗
PubMed1989

T cell responses in allergic rhinitis, asthma and atopic dermatitis.

Although clinical responses to allergens have been shown to primarily involve IgE antibodies, there is often no clear correlation between the amount of allergen-specific IgE present in the serum and the nature and severity of allergic symptoms. This observation raises the question of the possible role of non-IgE mediated types of immune responses in this reaction. It is not known to what extent components of T cell-mediated immunity are involved in IgE-mediated reactions but several observations suggest an association between atopic disease and alterations in cellular immune function. These include the frequent association of high serum IgE levels with: (i) several of the primary and acquired immunodeficiencies characterized by partial T cell deficiency; (ii) the defective cell-mediated immunity and resultant recurrent infections seen in the hyper-IgE syndrome; and (iii) the sudden rise in serum IgE levels associated with reduced numbers of suppressor T cells in bone marrow transplant recipients during the acute graft vs host disease. In this review, we will examine the recent evidence suggesting that the T lymphocyte may play a primary role in the pathogenesis of atopic disorders.

Antibodies↗
PubMed1988

Altered arachidonic acid metabolism and platelet size in atopic subjects.

The release and metabolism of endogenous arachidonic acid (AA) in physiologically activated platelets obtained from 11 atopic patients with allergic rhinitis and/or asthma was compared to that of sex- and age-matched nonatopic controls. Prelabeled [3H]AA platelets were stimulated with thrombin or collagen and the amount of free [3H]AA and radiolabeled metabolites released were measured by high-performance liquid chromatography. The results obtained indicate that although the incorporation of [3H]AA into platelet phospholipids and total release of 3H-radioactivity upon stimulation were comparable in the two groups, the percentage of 3H-radioactivity released from platelets as free AA was significantly lower (P less than 0.01) in the atopic group. The reduction in free [3H]AA was accompanied by an increase (P less than 0.01) in the percentage of 3H-radioactivity released as cyclooxygenase products in atopic platelets (compared to nonatopic cells) after stimulation with 10 and 25 micrograms/ml collagen. The amount of platelet lipoxygenase product released was comparable between the two groups. Although the blood platelet counts were similar, the mean platelet volume was statistically higher (P less than 0.01) in the atopic group. These results indicate that arachidonic acid metabolism in atopic platelets is altered, the pathophysiological significance of which remains to be clarified.

Adult↗
PubMed1988

Immunologic responses during allergen-specific immunotherapy for respiratory allergy.

At present there is no absolute way to determine which patient will respond to immunotherapy and which will not. Even in treated patients who derive clinical benefit, there is no one "best" immunologic parameter to follow although the generation of allergen-specific IgG seems to correlate better with clinical improvement than the other parameters. Whether or not the measurement of allergen-specific IgG4 will prove to be a useful clinical parameter is still a controversial issue and is an area for active investigation. The reason that IgG4 becomes elevated selectively over time during immunotherapy is not clear nor is its function known in the immune response to allergen. It is of interest however that IgG4 does not fix complement and may therefore account for the absence of immune complex disease in patients treated over many years. The modification of allergens through denaturization so that they are less reactive with preformed IgG has resulted in potent preparations that induce a strong IgG response. These preparations permit flexibility in dosage and in frequency of administration as well as produce no greater side effects than aqueous extracts. While these preparations would be a decided advantage over existing extracts, recent information that is accumulating regarding T cell recognition of antigen opens the way for more precise targeting of our therapy. That is, determination of the antigenic epitopes that trigger helper T cells should permit the construction of peptides that can "block" T cell recognition and potentially lead to immunologic unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1987

Effects of leukocyte inhibitory factor (LIF) on neutrophil mediated antibody-dependent cellular cytotoxicity.

The human lymphokine, leukocyte inhibitory factor (LIF), was investigated for its effect on neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) for K562 targets. Highly purified LIF (0.5 to 2 U/ml) induced a significant dose-dependent potentiation of neutrophil ADCC by up to 54.9% (p less than 0.001). Higher concentrations of LIF inhibited cytotoxicity. The degree of cytotoxicity was found to correlate (r = 0.99) with the increased secretion of superoxide after neutrophil-target cell interaction. Anaerobic conditions inhibited cytotoxicity mediated by both control and LIF-treated neutrophils. The latter observation lends support to the concept that enhanced ADCC was mediated through increased superoxide production and not through the induction of a separate pathway. Increased superoxide production may have resulted from an upregulation of the transduction mechanism leading to neutrophil stimulation through the Fc receptor. In addition, we demonstrated an increased capacity of the neutrophil to adhere to its target (average 3.3:1 effector:target ratio in untreated cells to 4.8:1 after treatment with LIF), and this may also have been responsible for the increase in the respiratory burst and subsequent enhanced ADCC. These observations provide potential support for an in vivo role for LIF in tumor immunity.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

Role of calcium in the activation of neutrophils by leukocyte inhibitory factor (LIF).

We investigated the role of calcium in the activation of neutrophils (PMN) by the human lymphokine leukocyte inhibitory factor (LIF). Using the fluorescent probe fura 2, we demonstrated that LIF (1/2-2 units) induced a small but significant dose-dependent increase in intracellular calcium in the presence of both calcium-containing (71 nM to 158 nM) and calcium-free (53 nM to 144 nM) buffer solutions. Thus, LIF is able to release calcium from both membrane channels and from intracellular stores. However, increases in intracellular calcium were not due to a release of Ca+2 from membrane stores, as shown by the inability of LIF to diminish fluorescence of the membrane-bound calcium probe chlortetracycline. In contrast to formyl-methionyl-leucyl-phenylalanine (fMLP), maximal calcium fluxes caused by LIF were of a much lower magnitude and not observed until 10-15 min after its application. The importance of calcium to the metabolic effects of LIF was demonstrated by the abilities of the calmodulin inhibitor trifluoroperazine (51.5% inhibition) and the extracellular calcium chelator EGTA (50.5% inhibition) to suppress LIF-mediated degranulation. The intracellular calcium chelator fura 2 also significantly inhibited LIF-mediated degranulation (61.8% inhibition). However, inhibition of the release of calcium from intracellular stores by TMB-8, had no effect on LIF-mediated degranulation. These data suggest that the ability of LIF to activate PMN is dependent on the availability of intracellular calcium and that this calcium is primarily derived from the slow influx of calcium from the extracellular pool.

Calcium↗
PubMed1978

Immunosuppressive characteristics of human AFP: effect on tests of cell mediated immunity and induction of human suppressor cells.

Murine AFP has been reported to be immunosuppressive in a variety of systems. However, the extent and degree of inhibition has varied in different species and laboratories. Therefore, we have examined the potential suppressive effect of purified human AFP on several in vitro tests of cellular immunity and the potential mechanism of its action. AFP purified from fetal and liver cancer sera significantly inhibited mitogen and antigen-induced proliferative responses but had no effect on lymphocyte E rosetting, MIF production or mitogen induced T cell cytotoxicity to Chang target cells. Purified human AFP induced human suppressor cell activity, capable of suppressing a one-way mixed lymphocyte reaction (MLC). In contrast to Con A induced suppressor cells, AFP induced suppressor cell activity was overcome by mitogen augmentation of the proliferative response in MLC. These data suggest that the inhibition of lymphocyte proliferation by human AFP may be mediated by the induction of a subpopulation of human suppressor cells. Furthermore, mitogen induced cell mediated cytotoxicity was partially inhibited by primary liver cancer serum and completely inhibited by newborn cord serum, in contrast to purified fetal or tumor AFP which had no effect. These data suggest that there are other immunosuppressive factors in fetal and tumor serum which require further characterization. These other serum factors may be responsible for some of the immunosuppressive effects attributed to AFP. Although AFP is unlikely to play a major immunosuppressive role physiologically in vivo, its selective effect on proliferative responses, apparently mediated by suppressor cells, may prove to be a useful pharmacologic probe of the mechanism of these in vitro lymphocyte responses and biological interactions.

Humans↗
PubMed1978

Human leukocyte inhibitory factor (LIF): a lymphocyte mediator with esteratic properties.

Sensitized human or guinea pig lymphocytes stimulated by specific antigen or nonspecifically by mitogens elaborate a soluble leukocyte inhibitory factor (LIF) that selectively inhibits the random migration of polymorphonuclear (PMN) leukocytes. LIF has the properties of a protein and is unique among lymphocyte mediators because of its esterase nature. While its natural substrate on PMN leukocytes is unknown, a synthetic amino acid derivative ([3H]benzoyl arginine ethyl ester) has been shown to be capable of serving as an artificial substrate. Through the use of selective esterase inhibitors it may eventually be possible to develop a biochemical assay for its detection in lieu of the biologic assay. LIF-containing supernatants have been shown to enhance a number of PMN leukocyte functions, including adherence, phagocytosis, metabolism, and electrophoretic mobility. In a chemotactic assay, LIF was found to induce the release of a low molecular weight peptide (neutrophil immobilization factor) from PMN leukocytes which decreased their spontaneous random movement and directed movement in the presence of a chemoattractant. This latter pathway may provide an amplification of LIF activity on the migration of PMN leukocytes.

Animals↗
PubMedDate not supplied

Nasal eosinophilia in allergic and nonallergic rhinitis: usefulness of the nasal smear in the diagnosis of allergic rhinitis.

Diagnostic nasal cytology has been advocated for use in distinguishing allergic from nonallergic rhinitis. We sought to determine prospectively the frequency of nasal eosinophilia (NE) in 100 patients in whom having allergic rhinitis (AR), nonallergic rhinitis, and other atopic conditions not involving the respiratory tract have been diagnosed. A nasal smear was obtained from consenting adults using the Rhino-Probe curette. Patients taking local or systemic corticosteroids, those with chronic rhinitis associated with aspirin sensitivity, and those with sinusitis were excluded. All cytograms were coded and read by a single "blinded" investigator. NE was considered significant if greater than 20% of sampled cells were eosinophils. Twenty-six of 61 (43%) patients with AR had NE. No NE was detected in the control population or in the skin test negative group of patients in whom having nonallergic rhinitis was diagnosed. One of 16 patients with allergic disease not involving the respiratory tract exhibited NE; this patient had atopic dermatitis with peripheral eosinophilia. No cases of eosinophilic nonallergic rhinitis were detected. There was no significant correlation of symptoms or the number of positive skin tests with NE. These data suggest that the nasal smear for eosinophils is an insensitive but specific test for the diagnosis of allergic rhinitis, when patients with nasal polyposis and aspirin sensitivity and/or negative skin tests are excluded.

Adult↗