Biomedical subjects

R A Musson

Publications and source records attributed to R A Musson.

22 records · Page 2Linked to original sources

PubMed1978

Distribution of endotoxin (lipopolysaccharide) in the tissues of lipopolysaccharide-responsive and -unresponsive mice.

We examined the distribution of bacterial lipopolysaccharide (LPS) in LPS-responsive (C3H/St) and LPS-unresponsive (C3H/HeJ) mice. The results reported here demonstrate that the rates of removal of an immunological or a toxic dose of LPS from the circulation are the same in both strains of mice. C3H/St spleens accumulated significantly more LPS than C3H/HeJ spleens after the intravenous injection of either an immunogenic or a toxic dose of LPS. There was also a greater amount of LPS associated with cells teased from C3H/St spleens compared to those from C3H/HeJ spleens. After a toxic dose of LPS, there was more LPS in C3H/St lymph nodes, adrenals, lungs, kidneys, and heart than in the corresponding C3H/HeJ tissues. The accumulation of more LPS in tissues from C3H/St mice compared to C3H/HeJ mice suggests that these tissues are involved in the pathophysiological and, ultimately, the toxic effects of LPS. The differential accumulation of LPS in the tissues of these two strains may be the reason for the decreased responses of C3H/HeJ mice to LPS.

Animals↗

PubMed1977

The role of an activatable esterase in immune-dependent phagocytosis by human neutrophils.

Diisopropylphosphofluridate, cyclohexyl alkylphosphonofluoridates, and cyclohexyl phenylalkylphosphonofluoridates, which are potent, irreversible inactivators of serine esterases, inhibit the phagocytosis of opsonized sheep erythrocytes by human neutrophils. Two types of inhibition were observed: a) 'cell-dependent' inhibition, which is determined by measuring the ingestion of neutrophils pre treated with the esterase inhibitors and washed; and b) 'phagocytosis-dependent' inhibition, which is due to the presence of the inhibitors during phagocytosis. With the cyclohexyl alkylphosphonofluoridates, phagocytosis-dependent inhibition was always greater than cell-dependent inhibition. Cell-dependent inhibition was irreversible and dependent on the duration of the incubation of neutrophils with inhibitor. Both types of inhibition were dependent on the concentration of the inhibitor. Poorly or non-phosphorylating analogues of the cyclohexyl alkylphosphonofluoridates of DFP were not inhibitory; nor did fluoride, the hydrolysis product of these inhibitors, inhibit ingestion under either condition. In addition, neither method of treating the neutrophils resulted in a decrease in neutrophil viability. Furthermore, pretreating the EAC1423 with the inhibitors did not decrease ingestion. We conclude that cell-dependent inhibition is due to the inactivation of an esterase required for phagocytosis which is in or on the neutrophil in an active form, and thus is susceptible to inhibition by the esterase inactivators before contact of the neutrophil with the phagocytic stimulus. Phagocytosis-dependent inhibition is interpreted as being due to inactivation of an esterase required for phagocytosis which is normally in an inactive precursor proesterase form that is activated by the interaction of the neutrophil with the phagocytic stimulus. The distinctly different inhibition profiles of the active and activatable esterases indicate that they are two different activities.

Cell Adhesion↗

PubMed1976

The inhibitory effect of chemotactic factors on erythrophagocytosis by human neutrophils.

The effect of various chemotactic factors on phagocytosis of sheep erythrocytes sensitized with IgG and complement (EAC1423) by human neutrophils (PMN) was studied. The bacterial chemotactic factor, a butanol extract of an Escherichia coli culture filtrate, the pronase sensitive and insensitive chemotactic substances isolated from this extract, C5a, a chemotactic fragment of the fifth component of complement, and a chemotactic synthetic peptide, formlymethionyl-leucine all significantly reduced the initial rate of ingestion at concentrations that are chemotactic for PMN. The bacterial chemotactic factor produced a 45 to 75% decrease in the initial rate of ingestion, but did not affect adherence of the EAC1423 and PMN. This same substance had no consistent effect on the total number of EAC1423 ingested at 90 min or longer or on the time interval from the addition of the EAC1423 to the start of ingestion. The inhibitory effect of the bacterial factor increased as the amount of bacterial factor was increased and the inhibitory effect was reversible. Inhibition by bacterial factor could be decreased by increasing the concentration of EAC1423; and if the concentration was increased 3-fold, the inhibition was abolished. These results suggest that inhibition by bacterial factor is competitive in nature.

Cell Adhesion↗

PubMed1972

Contact regions for dinitrophenyl and menadione haptens in an immunoglobulin binding more than one antigen.

Protein 460 is a mouse myeloma gamma A(2) protein that competitively binds two small haptens, 2,4-epsilon-dinitrophenyl-L-lysine (Dnp-Lys) and 2-methyl-1:4-naphthaquinone thioglycollate (MenTG), to the antibody-combining region. The intact protein has a relatively inaccessible sulfhydryl group on each heavy chain. When it is substituted with a bulky reagent the binding affinity for MenTG decreases, while the binding of Dnp-Lys remains the same. Guanidine.HCl selectively reduces binding of Dnp-Lys; dimethylsulfoxide selectively reduces binding of MenTG. Papain digestion of protein 460 followed by column chromatography gave two fractions: one contained both binding activities and the other contained the sulfhydryl group. The affinity for Dnp-Lys of the first fraction is the same as that of the whole molecule, while affinity for MenTG is decreased. Since selective alteration of one or the other binding activity can occur in different ways, it seems likely that even though the haptens compete with each other, there is some spatial separation between the groups of contact amino-acid residues involved in the binding of these two haptens. These findings do not support the hypothesis that an immunoglobulin molecule carries combining sites complementary only to a single hapten or to a structurally related series of haptens, but rather suggests that the antibody-combining site may be a polyfunctional region capable of binding several structurally dissimilar haptens. We discuss a mechanism whereby polyfunctional combining sites can give rise to an antibody population (immune serum) that has a high degree of specificity to a single hapten.

Alkylation↗