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D C Morrison

Publications and source records attributed to D C Morrison.

At least 73 records · Page 4Linked to original sources
PubMed1993

Evidence that lipopolysaccharide and pertussis toxin bind to different domains on the same p73 receptor on murine splenocytes.

In previous studies, we used a photoactivable, radioiodinated lipopolysaccharide (LPS) derivative to define and characterize a specific bacterial endotoxic LPS-binding protein (p73) on mammalian lymphoreticular cells, including B and T lymphocytes and macrophages. More recently, using the same methodology, we characterized a specific interaction of LPS with the S2 subunit of Bordetella pertussis pertussis toxin (PT) in the fluid phase (M.-G. Lei and D. C. Morrison, J. Biol. Chem., 268:1488-1493, 1993). Furthermore, we showed that lysozyme (LZM) but not polymyxin B can compete with PT for binding to LPS in the fluid phase, a result suggesting that these two molecules compete for the same binding site on LPS. In this report, we demonstrate that the binding of PT to murine splenocytes (cell-bound PT) reduces the ability of the LPS photo-cross-linking probe to bind to the p73 receptor. The reduction can also be demonstrated with the PT B oligomer, a result indicating that the observed reduction of LPS binding to the p73 receptor by PT is A-protomer (S1-subunit) independent. More importantly, our studies document that cell-bound PT can be radiolabelled by the LPS probe, coincident with the observed reduction in p73 photoaffinity labelling. The preferential interaction of LPS with the PT S2 subunit in the fluid phase was, however, not observed with cell-bound PT. The reduction in radiolabelling of the p73 receptor by the LPS probe and in radiolabelling of cell-bound PT was shown to be concentration dependent. The data presented here document, however, that LZM does not reduce the ability of the LPS probe to bind to the p73 receptor on mouse splenocytes, nor does the presence of LZM bound to LPS influence the observed reduction in photoaffinity labelling of p73 by the LPS probe or radiolabelling of cell-bound PT by the LPS probe. Collectively, these results support the concept that the ability of LPS to interact with PT in the fluid phase is not responsible for the ability of cell-bound PT to influence the binding of the LPS probe to the p73 receptor. Thus, it is suggested that PT and LPS bind to different sites on the p73 molecule and that this same p73 protein may recognize both LPS and PT.

Animals↗
PubMed1993

An interleukin-6-induced acute-phase response does not confer protection against lipopolysaccharide lethality.

Lipopolysaccharide (LPS), a component of gram-negative bacterial outer cell walls, can stimulate lymphoreticular cells to produce cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6. One of these proinflammatory cytokines, IL-6, induces hepatic synthesis of a class of proteins termed acute-phase proteins. D-Galactosamine inhibits acute-phase protein synthesis and concurrently sensitizes mice to a lethal dose of LPS approximately 10,000-fold. From these observations, we hypothesized that the acute-phase response may serve as a defense mechanism for protection of the host against the deleterious effects of LPS. To test this hypothesis, murine recombinant IL-6 (mrIL-6) was used to induce an acute-phase response prior to a lethal LPS challenge in both D-galactosamine-treated and normal mice. Induction of the acute-phase response by mrIL-6 was quantitated by measuring the concentrations of fibrinogen and complement component C3, two well-characterized acute-phase proteins, in the circulation. The effect of acute-phase and normal serum on TNF-alpha release by peritoneal macrophages stimulated with LPS in vitro was also examined. The results of these studies confirmed the induction of the acute-phase response by mrIL-6, as reflected in an approximate doubling in circulating levels of fibrinogen and C3. However, when either D-galactosamine-sensitized or normal mice were challenged with a lethal dose of LPS at various times after mrIL-6 administration, the acute-phase response induced by mrIL-6 did not alter either cumulative lethality or the kinetics of lethality. Additionally, compared with normal serum, acute-phase serum did not affect TNF-alpha release by peritoneal macrophages following LPS-mediated stimulation in vitro. Collectively, these studies would not support a dominant role for an IL-6-mediated acute-phase response as contributing to the resistance of normal mice compared with D-galactosamine-sensitized mice in LPS-induced lethal toxicity.

Acute-Phase Reaction↗
PubMed1992

Cytotoxic activity and production of toxic nitrogen oxides by macrophages treated with IFN-gamma and monoclonal antibodies against the 73-kDa lipopolysaccharide receptor.

The hamster IgM mAb 5D3 is specific for an 73-kDa LPS receptor on murine leukocytes. This mAb inhibits binding of radiolabeled LPS to splenocytes and acts as an agonist for induction of LPS-mediated changes in macrophage function. Resident peritoneal macrophages treated with IFN-gamma and mAb 5D3 developed potent cytotoxic activity against tumor cells. Cells treated with IFN-gamma or mAb 5D3 alone were inactive. Macrophage cytotoxic activity induced by IFN-gamma and mAb 5D3 was inhibited by NGMMLA and coincident with high levels of NO2-released into culture fluids. These data show that mAb 5D3 serves as an effective trigger signal for induction of cytotoxic activity with IFN-gamma-primed macrophages. Indeed, mAb 5D3 exactly mimicked the effects of LPS in these same systems. Unlike LPS, effects of mAb 5D3 on induction of macrophage cytotoxic activity and production of nitrogen oxides was abrogated after boiling, and not affected by addition of polymyxin B. The effects of LPS and mAb 5D3 as a trigger signal for IFN-gamma-primed macrophages were associated with production of TNF activity in culture fluids and inhibited by mAb against rTNF-alpha. Expression of class II MHC on macrophages induced by IFN-gamma treatment was suppressed by both LPS and mAb 5D3. These suppressive effects of LPS and mAb 5D3 were not affected by NGMMLA or mAb against rTNF-alpha. Finally, macrophages treated with LPS or mAb 5D3 before exposure to IFN-gamma and LPS or mAb 5D3 did not develop cytotoxic activity or high levels of NO2- in the culture fluids. These same cells developed both effector activities after addition of rTNF-alpha. These results in toto identify the 73-kDa protein as a receptor that mediates LPS-induced changes in macrophage effector function. The mAb 5D3 serves as a specific and defined reagent agonist for analysis of LPS receptor-linked change.

Animals↗
PubMed1992

Detection and analysis of the 80-kd lipopolysaccharide receptor in macrophages derived from Lpsn and Lpsd mice.

An 80-kd lipopolysaccharide (LPS)-binding protein with specificity for the lipid A region has been identified on lymphocyte and macrophage membranes. In an attempt to gain insight into the hyporesponsiveness of C3H/HeJ (Lpsd) mice to LPS, an affinity-purified rabbit polyclonal IgG with specificity for this receptor was used to compare the expression and distribution of the 80-kd LPS receptor on thioglycollate-elicited peritoneal macrophages derived from normal (Lpsn) and (Lpsd) mice. By enzyme-linked immunosorbent assay, immunofluorescence microscopy, and flow cytometry, macrophages from Lpsn and Lpsd mice showed comparable expression of the 80-kd LPS receptor, although only a subpopulation of macrophages from both strains express it. Macrophages from both strains showed indistinguishable surface distribution of the 80-kd LPS receptor, as determined by confocal microscopy and analysis using an anchored cell analysis station. Treatment of macrophages with interferons, protein-rich LPS, or glucocorticoids, agents known to modulate a variety of macrophage cell surface markers and receptors, failed to alter expression of the 80-kd receptor. These findings support the hypothesis that the hyporesponsiveness of the Lpsd mouse strains to LPS is not due to an absence of receptors but rather is distal to binding of LPS and most likely attributable to a failure of these macrophages to transduce the signal derived at the cell surface to the interior of the cell.

Animals↗
PubMed1992

Lipopolysaccharide receptors and signal transduction pathways in mononuclear phagocytes.

There is little question but that bacterial lipopolysaccharides (LPS) remain one of the most potent stimuli which can affect macrophage activation. Although the precise biochemical mechanisms responsible for this remain to be fully defined, there is now evidence accumulating from a number of laboratories that functional receptors for these bacterial products do exist and may contribute to the initial triggering event. Unfortunately, there is currently no consensus as to which of the candidate receptors identified to date serves as the primary binding target for LPS, and it is possible that the difference in macrophage cell types, LPS probes, and detection systems will all influence the nature of the binding. At the present time, therefore, macromolecules of 96-kDa, 95-kDa (adhesion beta chain), 80-kDa, 65-kDa, and 55-kDa may be considered as possible LPS targets. With the exception of the 96-kDa protein identified by Hampton and his co-workers, there exists some experimental evidence for a functional role for each of the molecules so far identified. It is apparent that the molecular cloning and sequencing and subsequent biochemical characterization of these LPS receptors will be required to determine unequivocally their role in LPS-mediated triggering events. Such information will be invaluable in sorting out the relevant biochemical second signals involved in macrophage activation. Although much new information has recently been accumulated on potential signaling pathways for LPS, the definitive events remain far from unequivocally established. In view of the obvious importance of LPS-macrophage interactions in the overall capacity of the mammalian host to respond appropriately to the potentially hostile prokaryotic environment, a precise delineation of LPS-mediated macrophage activation is critical to our understanding of this important inflammatory mediator cell.

Animals↗
PubMed1992

Tumor necrosis factor-alpha gene expression in the tissues of normal mice.

Although TNF-alpha is traditionally associated with macrophage activation during neoplasia and acute inflammation, recent Northern blot hybridization studies indicate that gene expression occurs in the absence of pathology. In order to identify the cellular sources of endogenous message and protein, normal mouse tissues were tested for TNF-alpha mRNA using in situ hybridization and for the corresponding protein by immunocytochemistry. Unexpectedly, specific TNF-alpha message was readily detected in hepatocytes, kidney tubule epithelial cells, various populations of spleen cells and neurons. TNF-alpha protein was present in the same liver and kidney cells as those that contained TNF-alpha mRNA, was low in spleen cells, and was absent in neurons. These results suggest that cells other than macrophages are the major sources of TNF-alpha gene products in normal tissues, indicate that regulation is accomplished by more than one mechanism, and are consistent with the postulate that products of this gene contribute to normal physiological processes.

Animals↗
PubMed1992

Identification and characterization of lipopolysaccharide-binding proteins on human peripheral blood cell populations.

Previous research in this laboratory, using photoactivatable radioiodinated lipopolysaccharide derivatized with sulfosuccinimidyl-2-(p-azidosalicylamide)-1,3'-dithiopropionate (125I-ASD-LPS), has resulted in the identification of a specific LPS receptor with a molecular mass of approximately 73 kDa on murine lymphocytes and splenic macrophages. The experiments presented in this report investigated whether a similar LPS-binding protein was also expressed on human peripheral blood populations, including monocytes, lymphocytes, neutrophils, platelets, and erythrocytes. Each cell population was incubated with 125I-ASD-LPS, UV irradiated, washed, reduced, and solubilized, and the cell lysates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. On all of the cell populations, except erythrocytes, a similar 73-kDa LPS-binding protein was present. In addition, each population also expressed lower-molecular-weight secondary LPS-binding proteins, some of which were conserved among the populations. Binding of the photoactivatable LPS probe was found to be both time and temperature dependent. These data support the concept that the 73-kDa LPS-binding protein is conserved on multiple cell types from a variety of species.

Acute-Phase Proteins↗
PubMed1991

Specific endotoxic lipopolysaccharide-binding receptors on murine splenocytes. III. Binding specificity and characterization.

In previously published studies, we employed a photoreactive radioiodinated derivative of LPS from Escherichia coli 0111:B4 to identify and characterize a membrane-localized specific LPS binding protein of approximately 80-kDa molecular mass. Our more recent studies demonstrating that mAb with specificity for this 80-kDa protein will act as an agonist in mediating macrophage activation have established that this protein serves as a specific receptor for LPS. In the experiments reported here, we have more accurately determined the apparent molecular mass of this protein to be 73 kDa (p73). We have also extended the sources of LPS-derivatized photo-cross-linking preparations (including Re-LPS) to determine generality of LPS binding to this receptor. Binding to the p73 LPS receptor is demonstrated with all of the LPS derivatives synthesized in our laboratory, as well as probes synthesized by other investigators. Binding of S-LPS is readily inhibited by Re chemotype LPS, and we have shown that this competitive inhibition is most likely not the result of formation of LPS aggregates. These results confirm and extend our earlier studies suggesting that the binding of LPS to the p73 receptor is lipid A specific. We further demonstrate that, in contrast to results published in a recent report, the p73 LPS receptor has no significant binding specificity for a variety peptidoglycan polymer preparations. Finally, we show that this LPS receptor can be detected on murine fibroblast, macrophage, and mastocytoma cell lines. Differences have been observed in the level of expression of LPS receptors on the various cell lines studied.

Animals↗
PubMed1991

Modeling of T cell contact-dependent B cell activation. IL-4 and antigen receptor ligation primes quiescent B cells to mobilize calcium in response to Ia cross-linking.

The generation of antibody secretory cells from resting B lymphocytes after immunization with most protein Ag requires B cell signaling by Ag, direct Th cell contact and lymphokines. Previous studies suggest that cell contact-mediated signals may be transduced by Ia after Ia binding by alpha beta TCR and/or CD4. Seemingly inconsistent with this concept are findings that cross-linking of Ia molecules on quiescent B cells leads to cAMP generation that is antagonistic for B cell mitogenesis. Here we show that ligand binding to IL-4 and Ag receptors on quiescent B cells induce transition of these cells into a competent state in which Ia molecules transduce signals via a distinct mechanism. This mechanism involves the tyrosine kinase-dependent activation of phospholipase C leading to Ca2+ mobilization from intracellular stores and the extracellular space. This competence, which is seen within 4 h of priming, is not simply a function of increased Ia expression by the B cell because the response can be induced by cross-linking of less than 5% of cell surface Ia molecules on primed cells. Finally, cross-linking of Ia molecules leads to more than fivefold greater increase in [Ca2+]i than is induced by membrane Ig ligation. These findings are consistent with alpha beta TCR/CD4 delivery via Ia of proliferative signals mediated by tyrosine kinase activation, phosphoinositide hydrolysis and Ca2+ mobilization.

Animals↗
PubMed1991

Hydrazine sulfate protects D-galactosamine-sensitized mice against endotoxin and tumor necrosis factor/cachectin lethality: evidence of a role for the pituitary.

In previously published studies, we had demonstrated that hydrazine sulfate pretreatment protected mice against the lethal effects of endotoxin and that this protection was accompanied by a sustained increase in hepatic phosphoenolpyruvate carboxykinase activity (Silverstein, R., C.A. Christoffersen, and D.C. Morrison. 1989. Infect. Immun. 57:2072). The same hydrazine sulfate pretreatment has now been found to protect mice against endotoxin in the D-galactosamine model with an increase in the endotoxin LD50 of approximately four orders of magnitude. Elimination of the pretreatment period, or administration of an additional dose of D-galactosamine at the time of hydrazine sulfate pretreatment, renders the mice refractory to the protection. Given the sensitivity of phosphoenolpyruvate carboxykinase regulation to several hormones, we investigated the possibility that protection may have been hormone mediated. In addition to determining the effect of hydrazine sulfate on the plasma levels of phosphoenolpyruvate carboxykinase regulating hormones, we have investigated the effects of hydrazine sulfate on endotoxin lethality in mice whose capacity to respond hormonally to external stimuli has been compromised by hypophysectomy. Our results show a significant enhancement in circulating levels of plasma corticosterone 30 min after hydrazine sulfate injection. Moreover, hypophysectomy results in a marked increase in sensitivity of mice to endotoxin challenge as well as an abrogation of the protection against endotoxin lethality mediated by hydrazine sulfate. Although hydrazine sulfate protection distinguishes between sensitivity brought on, individually, by D-galactosamine and by hypophysectomy, mice sensitized by both hypophysectomy and D-galactosamine are not protected against endotoxin lethality by hydrazine sulfate. We conclude that hydrazine sulfate protection against endotoxin lethality is endocrine dependent, with the available evidence implicating a pituitary/adrenal axis, with glucocorticoid involvement. In as much as D-galactosamine is known to act directly in the liver in disrupting protein synthesis, it is proposed that events in the liver are critical to the hydrazine sulfate-mediated protection against endotoxin and are possibly the target of the endocrine involvement. Hydrazine sulfate pretreatment also protects D-galactosamine-sensitized mice against the lethal effects of injected tumor necrosis factor/cachectin.

Animals↗
PubMed1991

Lactoferrin-lipopolysaccharide interactions. Effect on lactoferrin binding to monocyte/macrophage-differentiated HL-60 cells.

Lactoferrin (LF) has been implicated in a number of functions including the negative regulation of myelopoiesis in vitro and in vivo, an effect mediated by suppression of cytokine release from monocytes/macrophages. This suppression is abrogated by bacterial LPS. In the present study, HL-60 cells were induced to differentiate to monocytes/macrophages by 12-O-tetradecanoyl phorbol-13-acetate, and LF-binding assays were performed. After differentiation, HL-60 cells showed a twofold increase of LF-binding sites with no difference in the specificity or affinity of LF between pre- and post-differentiated cells. CD11a, CD11b, and CD11c Ag, which have been associated with specific binding sites for LPS on monocytes/macrophages, were also increased three- to fourfold after differentiation. With the use of this system, the effect of LPS on LF binding was studied. At 37 degrees C, LPS enhanced LF binding on HL-60 cells, especially after differentiation. Conversely, at 4 degrees C, LPS inhibited LF binding. There was little effect of temperature on LF binding in the absence of LPS. In the presence of polymyxin B sulfate, the enhanced LF binding by LPS was abrogated. Also, pretreatment with mAbCD11 and/or mAb5D3, which are associated with or directed against candidate LPS receptors, reduced LF binding. Cross-linking studies using an iodinated, photoactivatable LPS derivative ([125I]ASD-LPS) demonstrated directly the specific binding of LPS to LF. These data indicate a dichotomous nature of LF binding on monocyte/macrophage-differentiated HL-60 cells--one being mediated by specific LF receptors whereas the other is apparently mainly via LPS receptors after formation of an LF-LPS complex. These interactions, for which a model is proposed, help to explain the mechanism behind LPS abrogation of the myelopoietic suppressive effects of LF, and a situation that probably occurs during bacterial infection.

Affinity Labels↗
PubMed1991

Postprandial thermogenesis in post-obese women and weight-matched controls.

Postprandial thermogenesis was assessed on two occasions in six weight-stable post-obese women, with a mean weight loss of 21.9 (range 10.1-43.3) kg, and six control subjects who had never been overweight. The two groups of subjects were closely matched for weight, height, body mass index and age. The energy load of the test meal was proportional to each subject's energy requirement. Energy expenditure was monitored for 40 min before and 245 min after the meal by ventilated hood indirect calorimetry. Mean baseline energy expenditure was 3.65 (s.e.m. 0.22) kJ/min in the post-obese, and 3.73 (s.e.m. 0.17) kJ/min in the control subjects (P greater than 0.5). Mean postprandial energy expenditure was 4.50 (s.e.m. 0.25) kJ/min in the post-obese women and 4.61 (s.e.m. 0.18) kJ/min in the control women (P greater than 0.5). The mean thermic response, expressed as percentage of baseline energy expenditure, was 23.5 per cent (s.e.m. 1.4 per cent) in the post-obese and 24.1 per cent (s.e.m. 1.6 per cent) in the control subjects (P greater than 0.5). When expressed as percentage of the meal energy, the response was 7.9 per cent (s.e.m. 0.4 per cent) in the post-obese, and 7.4 per cent (s.e.m. 0.4 per cent) in the control subjects (P greater than 0.1). Reproducibility of duplicate measurements of postprandial thermogenesis, estimated as within-subject coefficient of variation, was 16.6 per cent when expressed as percentage increase over baseline energy expenditure, and 16.4 per cent when expressed as percentage of meal energy ingested. The present results do not support an impaired postprandial thermogenesis in women with a tendency to obesity, and suggest that part of the controversy in this field may be due to differences in study design and to the poor reproducibility of this measurement.

Adult↗
PubMed1990

Activation of C3H/HeJ macrophage tumoricidal activity and cytokine release by R-chemotype lipopolysaccharide preparations. Differential effects of IFN-gamma.

We have investigated the relative immunostimulatory activities of S-chemotype LPS and R-chemotype LPS preparations on C3H/HeJ peritoneal macrophages in vitro. As assessed by either secretion of TNF-alpha or IL-1, some of the R-chemotype LPS manifest significant activity on these normally LPS-unresponsive cells. The expression of IL-1 activity by R-LPS-stimulated C3H/HeJ macrophages was unaffected by IFN-gamma; however, this cytokine significantly enhanced TNF-alpha production by the same cells. The R-chemotype LPS preparations alone were not able to activate C3H/HeJ macrophages to become tumoricidal but activity could readily be demonstrated in the presence of IFN-gamma. Of potential importance is the observation that the profile of relative activity of the various R-chemotype LPS preparations for macrophage activation does not parallel that previously obtained by us for the C3H/HeJ B-lymphocyte activation.

Animals↗
PubMed1990

Generation and characterization of hamster-mouse hybridomas secreting monoclonal antibodies with specificity for lipopolysaccharide receptor.

Experiments are described for the partial purification of the 80-kDa LPS binding protein expressed on macrophages and lymphocytes. This partially purified Ag was used to immunize adult Armenian hamsters and splenocytes from immunized animals were fused with murine myeloma cell lines. Hybridoma cell culture supernatants containing mAb were screened by ELISA for positive binding to the immunizing Ag, murine splenocytes and the murine 70Z/3 pre B cell and for an absence of binding to sheep E. Positive clones were further screened for reciprocal competitive binding with LPS on spleen cells and ability to modulate B lymphocyte mitogenic activity. Two hybridoma cell lines secreting IgM monoclonals, termed mAb3D7 and mAb5D3, were identified that satisfied all of the selection criteria. These hybridoma cell lines were subcloned and expanded. Binding of one (mAb3D7) was abrogated by treatment of Ag with mild periodate; binding of the second (mAb5D3) was destroyed by digestion of Ag with proteinase K. Binding specificity for mAb5D3 has been confirmed by ELISA using highly purified 80-kDa protein. These mAb have been of value in establishing that the 80-kDa LPS binding protein previously identified may serve as a specific functional receptor for LPS.

Animals↗
PubMed1990

Induction of macrophage-mediated tumor cytotoxicity by a hamster monoclonal antibody with specificity for lipopolysaccharide receptor.

Experiments have been carried out to assess the immunostimulatory activity of a hamster IgM mAb (mAb5D3) with specificity for an 80-kDa LPS-binding protein expressed on murine macrophages and monocytes. The addition of mAb5D3 to cultures of murine bone marrow-derived macrophages activated these cells to become tumoricidal for mastocytoma cells in vitro. The activity of mAb5D3 was enhanced in the presence of IFN-gamma. Neither mAb5D3 nor LPS were able to activate macrophages from the LPS-hyporesponsive C3H/HeJ mouse, although these cells responded normally to heat-killed Listeria monocytogenes. The results of several experiments establish that the observed LPS-like activity of mAb5D3 was not due to contaminating endotoxin: 1) the activity of mAb5D3 but not LPS was heat labile at 100 degrees C; 2) the activity of LPS but not mAb5D3, was inhibited by addition of polymyxin B; and 3) quantitative estimates of endotoxin contamination by Limulus amoebocyte lysate reactivity. These experiments thus demonstrate that mAb5D3 can serve as an agonist for LPS-dependent macrophage responses and, when considered with those of our companion paper showing specificity of mAb5D3 for the 80-kDa LPS-binding protein, provide strong support for the concept that the 80-kDa LPS-binding protein previously identified serves as a functional receptor for LPS on murine macrophages.

Animals↗
PubMed1990

Dual molecular mechanisms mediate ligand-induced membrane Ig desensitization.

We have previously shown that ligation of murine B cell membrane IgM or IgD can lead to inactivation of the signal transducing ability of unligated Ag receptors. We describe further studies of the molecular basis of this desensitization. Consistent with the possibility that ligand induced desensitization is mediated by protein kinase C (PKC) are findings that demonstrate that both Ig binding ligands and PKC activators (DIC8 or PMA) induce desensitization in virtually all resting B cells. However, ligand-induced desensitization is longer lived than PMA- or DIC8-induced desensitization and insensitive to the PKC inhibitor staurosporine. Further, biochemical studies indicate that insufficient PKC activation is induced by ligation of membrane Ig to mediate the observed desensitization. Thus data indicate that PKC must play only a minor role in ligand-induced membrane Ig desensitization. Further studies explored the molecular source and target of effectors that mediate ligand-induced desensitization. Data indicate that phosphoinositide hydrolysis is neither necessary nor sufficient for ligand induction of desensitization. Finally, ligand-induced desensitization appears to be mediated by uncoupling of membrane Ig from G proteins that regulate phospholipase C because ligand desensitized cells are hyperresponsive to agents including ALF4- and mastoparan which activate G proteins leading to mobilization of Ca2+. Thus, the function of G proteins and further downstream elements that mediate Ca2+ mobilization is intact. Taken together, these data are most consistent with ligand-induced membrane Ig desensitization being mediated by a non-PKC, non phosphatidylinositol 4,5-bisphosphate hydrolysis involving mechanism that has as its target a structure that is very proximal to the receptor, such as the receptor itself or a transducer complex analogous to CD3.

Amino Acid Sequence↗