Biomedical subjects

A L Sandberg

Publications and source records attributed to A L Sandberg.

At least 55 records · Page 3Linked to original sources

PubMed1977

Prostaglandin regulation of macrophage collagenase production.

The production of collagenase (EC 3.4.24.3) by endotoxin-stimulated macrophages was significantly inhibited by indomethacin, indicating that prostaglandins (PGs) mediate this effect. Inhibitions of collagenase production by indomethacin was overcome by addition of exogenous PGE2 at 10 nM whereas the addition of 0.1 and 1.0 micrometer PGE2 increased the enzyme production to 3 times that achieved by endotoxin. Although the addition of prostaglandin alone to macrophage cultures did not stimulate collagenase production, the simultaneous addition of PGE1 or PGE2 and endotoxin enhanced collagenase activity 2- to 10-fold. This increase was detectable at PGE concentrations of 10 nM and was optimal at 0.1-1.0 micrometer. PGF2alpha had little effect on either the enhancement of collagenase production by endotoxin-stimulated macrophages or its restoration in cultures inhibited by indomethacin. Radioimmunoassay of prostaglandins in the culture media revealed that macrophages exposed to endotoxin secreted 40-fold more PGE2 than did unstimulated cells. The increase in PGE2 was detected 4 hr after exposure to endotoxin and was maximal at 14 hr. The peak PGE2 concentrations in the culture media were similar to those of exogenous PGE2 (about 10 nM) needed to restore collagenase production in indomethacin-treated cultures. These findings demonstrate the involvement of PGE in the endotoxin-activation of macrophages with resultant production of collagenase.

Cells, Cultured↗

PubMed1977

Initiation of bone resorption by the classical and alternative C pathways and its mediation by prostaglandins.

Activation of C by immunoglobulins reactive with cell surface antigens stimulated synthesis of prostaglandin E and resultant release of 45Ca from organ cultures of fetal rat bones labeled in utero. Absorption of the C source (rabbit serum) with rat spleen cells or dilution of C abolished this activity which was, however, restored by addition of immunoglobulin preparations from sera of rabbits immunized with either rat erythrocytes or sonicated fetal rat bones. The active reconstitution factors were present in the 50% (NH4)2SO4 cut of the antisera and were eluted from Sephadex G-200 in both the 19S and 7S fractions and from DEAE cellulose in the IgG-containing fraction. The C-dependent resorption of bone by the F(ab')2 fragments of the IgG antibody implicated a role for the alternative C pathway in this event. Complete inhibition of this biologic effect by indomethacin and detection of enhanced levels of prostaglandin E in the media of cultures containing antibody and C demonstrated a role for prostaglandins as mediators in the destruction of bone initiated by immune activation of C.

Animals↗

PubMed1976

Comparison of the pyrogenicity, Limulus activity mitogenicity and complement reactivity of several bacterial endotoxins and related compounds.

The correlation of mitogenicity, complement activation, pyrogenicity and Limulus amebocyte lysate (LAL) gelation induced by 17 bacterial endotoxins (LPS), modified endotoxins, related compounds, and other B cell mitogens was examined. With the use of these compounds, a significant correlation was found between pyrogenicity and mitogenicity (r = 0.85, p is less than 0.0005), pyrogenicity and LAL reactivity (r = 0.84, p is less than 0.0005), and mitogenicity and LAL reactivity (r = 0.72, p is less than 0.0025). In contrast, complement activation by these compounds did not correlate with mitogenicity, pyrogenicity or LAL reactivity (r = 0.09, p is greater than 0.4; r = -0.17, p is greater than 0.3; r = 0.17, p is greater than 0.3, respectively). These results suggest that a specific chemical configuration may induce mitogenicity, pyrogenicity, and LAL reactivity which differs from that responsible for complement activation.

Animals↗

PubMed1976

Interaction of soluble C3 fragments with guinea pig lymphocytes. Comparison of effects of C3a, C3b, C3c, and C3d on lymphokine production and lymphocyte proliferation.

C3a, C3b, C3c, and C3d were generated from purified guinea pig C3 by trypsin treatment. These fragments were characterized immunochemically and functionally by rosette inhibition. C3b is capable of binding to both C3b and C3d receptors on lymphocytes whereas C3d binds only to C3D receptors. C3b stimulates guinea pig spleen cells to elaborate a macrophage chemotactic factor which is similar in m.w. to that generated in response to PHA or LPS and is antigenically unrelated to C3 or C5. In contrast, neither C3a, C3c, or C3d stimulate guinea pig lymphocytes. Neither C3 nor any of its major fragments induce cellular proliferation. These data are compatible with the hypothesis that C3b triggers spleen cells to release a macrophage chemotactic factor by cross-linking C3b and C3d receptors.

Animals↗

PubMed1975

Lymphokine production by C3b-stimulated B cells.

Trypsin cleavage of guinea pig C3 (60 sec, 20 degrees C) yields a fragment which stimulates guinea pig lymphocytes to produce a chemotactic lymphokine. These digested C3 preparations possess only minimal inherent chemotactic properties. The response is completely inhibited by prior adsorption of the trypsin-derived C3 fragments with insolubilized anti-C3. The active C3 fragment is C3b as demonstrated by the elution of activity in the exclusion volume of Sephadex G-75 (m.w. greater than 50,000 dalton). The C3b-dependent cellular-derived chemotactic factor is present in the supernatants of B cell cultures and totally absent in those of T cell cultures. Generation of this lymphokine occurs in the absence of cellular proliferation.

Animals↗

PubMed1974

Complement-dependent stimulation of prostaglandin synthesis and bone resorption.

Complement-sufficient heterologous serum induced prostaglandin synthesis and resultant resorption in cultures of fetal rat long bones. Bone resorption was enhanced with unheated normal rabbit serum as compared to heated serum or serum from rabbits lacking the sixth component of complement (C6). Addition of functionally purified C6 restored resorptive activity in C6-deficient serum. Concentrations of prostaglandin E were increased in the culture media of bones incubated with complement-sufficient serum. The resorptive effects of active serum as well as the appearance of prostaglandin E in the media were inhibited by indomethacin.

Animals↗

PubMed1973