Interleukin-1 (IL-1), a modulatory protein with immune and inflammatory functions, is spontaneously released by tissue macrophages in lower concentrations compared with peripheral blood monocytes. Conversely, in idiopathic pulmonary fibrosis, sarcoidosis, and certain inflammatory diseases, increased amounts of IL-1 are released by alveolar macrophages (AM). We examined IL-1 production by AM from patients with adult respiratory distress syndrome (ARDS) and compared it with that in patients with severe pneumonia requiring assisted ventilation, patients with pneumonia requiring parenteral antibiotics, and healthy control subjects. In vitro, ARDS AM released significantly more total IL-1 and IL-1 beta than did ARDS AM in patients with pneumonia and in control subjects. Moreover, after stimulation of these cells with 10 micrograms/ml of lipopolysaccharide (LPS), ARDS AM significantly increased release of IL-1 and IL-1 beta. AM from patients with severe pneumonia also released greater amounts of both IL-1 and IL-1 beta as fresh explants and after LPS stimulation when compared with control subjects. Incubation of AM with 250 U/ml human interferon-gamma (gamma IFN) was associated with less IL-1 beta release. However, stimulating AM from patients with ARDS and severe pneumonia with gamma IFN plus LPS enhanced the release of IL-1 beta compared with that in patients with pneumonia and in control subjects. ARDS AM released significantly more IL-1 beta than did all of the other groups. These results demonstrate that AM from patients with ARDS are capable of releasing significantly greater amounts of IL-1, which may be related to the progression of acute lung injury.
Activated macrophages display a terminal galactopyranosyl group on their membrane surface that binds the lectin Griffonia simplicifolia-IB4 (GSIB4). Using FITC-conjugated GSIB4, we examined the induction and subsequent expression of this corresponding marker on peritoneal macrophages from normal (NMO) and LPS-treated (LPS MO) mice. Although the percentage of fresh LPS MO explants that bound GSIB4 was always higher when compared to the NMO counterparts, marker expression on the latter was readily enhanced by culturing the cells in vitro either alone or with stimuli. Moreover, we found that an increase in this activity was promoted by either nonspecific phagocytosis of latex beads, or gamma-interferon (gamma-IFN) treatment. Further investigation showed that a prerequisite sequence of signal delivery to the macrophages was associated with maximal expression of the GSIB4 binding. When gamma-IFN treatment preceded latex bead ingestion, maximum GSIB4 binding occurred. Data obtained from using short-term (1 hr) and long-term (24 hr) exposure to latex beads showed that metabolic processing of induction signals was required to enhance the response over time. This yielded better GSIB4-binding activity when responses to these pulses were analyzed in freshly explanted macrophages. The overall results of this study demonstrated that macrophage binding of GSIB4 was differentially associated with stimuli induction. Moreover, select signals in the form of soluble mediators, or the mechanical events characteristic of internalization were capable of eliciting an increase in the percentage of macrophages that were positive for binding GSIB4. Thus, the enhanced affinity for binding this lectin may serve as a useful marker to determine the magnitude of macrophage responsiveness when these cells are examined following their exposure to different stimuli.
CBMO, cord blood monocyte IFN-'Y, interferon-'Y TNF/cachectin constitutes one of the major inflammatory mediators secreted by activated monocytes and macrophages (I); it is implicated as a primary and proximal mediator ofendotoxic shock (2) and plays a physiologic role in inflammation. Receptors for the Fe domain of immunoglobulins are involved in the regulation of various monocyte/macrophage immune functions, including phagocytosis (3), antibody-dependent cell-mediated cytotoxicity (4), the clearance of immune complexes (5), and the secretion of inflammatory mediators (6). Among the secretory products induced by Fe interactions are leukotrienes (7), prostaglandins (8), various hydrolytic enzymes (9), and multiple cytokines, including IL-I (10), IL-6 (II), and TNF (12). Debets et al. (12) showed that when monocyte Fe receptors bound with cytophilic human IgG were cross-linked by the addition of antihuman IgG, rapid secretion of TNF was induced. These experiments were conducted with adherent adult human monocytes; soluble IgG alone failed to induce a response. In subsequent work, Debets et al. (13) demonstrated that cross-linking of FcR was not sufficient for the induction ofTNF but that high affinity Fc-FcR interactions are required. Kuhnert et al. (14) demonstrated the induction of TNF and
Macrophages (m phi) derived from mice treated in utero with chlordane show a significant delay of tumoricidal induction activity. In this study, m phi from chlordane-treated animals required a 48 h in vitro period of induction with interferon-gamma and lipopolysaccharide (IFN/LPS) before they could kill P815 targets. Similarly, m phi from chlordane-treated animals also failed to produce an immediate H2O2 burst upon perturbation. Conversely, their stimulated control m phi counterparts were tumoricidal by 2 h and exhibited a respiratory burst without any delay. Moreover, levels of the second messenger, inositol triphosphate (IP3), were significantly delayed in chlordane-treated animals following interaction with IFN/LPS. When nitrate/nitrite production was analyzed as an alternate mechanism for killing tumors, stimulated m phi from both normal and chlordane-treated animals responded equally. The data show that chlordane differentially introduces defects in m phi biochemical mechanisms associated with tumor killing.
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