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Biomedical subjects

M T Drayson

Publications and source records attributed to M T Drayson.

At least 19 recordsLinked to original sources
PubMed2006

Total serum IgE and IgE antibodies specific to house dust mite found in two aged-matched cohorts of children with and without otitis media with effusion.

OBJECTIVES: To determine whether otitis media with effusion (OME) is associated with elevated serum immunoglobulin E (IgE) and IgE specific for house dust mite. DESIGN: Forty-seven children who had evidence of bilateral OME, both otoscopically and on tympanometry, on two separate occasions, 3 months apart were admitted for ventilation tubes. Forty-eight children admitted for minor eye surgery who had otoscopically normal ears and no history of middle ear problems were used as controls. Bloods samples were taken under anaesthesia. Total IgE and IgE radioallergosorbent test (RAST) to house dust mite was measured by the Pharmacia Unicap 100 system. The results from the two groups were compared. SETTING: Birmingham Children's Hospital. PARTICIPANTS: Children between the ages of 3 and 10. Children with Down's syndrome, cleft lip and palate, ciliary abnormalities, known immunodeficiencies and cardiac abnormalities were excluded. MAIN OUTCOME MEASURES: Total IgE and RAST to house dust mite. A RAST of >0.35 was taken to be positive. RESULTS: There was no statistical difference between the control and study groups for the total IgE. Six children from both study and control groups had a raised house dust mite RAST. There was no difference in the levels between either group. CONCLUSIONS: Our findings indicate that there is no direct relationship between OME and biochemical evidence of allergy, specifically to house dust mite.

Allergens↗
PubMed2005

Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors.

Histone deacetylase inhibitors (HDIs) are a new class of drugs with significant antileukemic activity. To explore mechanisms of disease-specific HDI activity in acute myeloid leukaemia (AML), we have characterised expression of all 18 members of the histone deacetylase family in primary AML blasts and in four control cell types, namely CD34+ progenitors from umbilical cord, either quiescent or cycling (post-culture), cycling CD34+ progenitors from GCSF-stimulated adult donors and peripheral blood mononuclear cells. Only SIRT1 was consistently overexpressed (>2 fold) in AML samples compared with all controls, while HDAC6 was overexpressed relative to adult, but not neo-natal cells. HDAC5 and SIRT4 were consistently underexpressed. AML blasts and cell lines, exposed to HDIs in culture, showed both histone hyperacetylation and, unexpectedly, specific hypermethylation of H3 lysine 4. Such treatment also modulated the pattern of HDAC expression, with strong induction of HDAC11 in all myeloid cells tested and with all inhibitors (valproate, butyrate, TSA, SAHA), and lesser, more selective, induction of HDAC9 and SIRT4. The distinct pattern of HDAC expression in AML and its response to HDIs is of relevance to the development of HDI-based therapeutic strategies and may contribute to observed patterns of clinical response and development of drug resistance.

Acetylation↗
PubMed2004

Effect of prolonged exercise and carbohydrate ingestion on type 1 and type 2 T lymphocyte distribution and intracellular cytokine production in humans.

The present study was undertaken to examine the role of the exercise-induced stress hormone response on the regulation of type 1 and type 2 T lymphocyte intracellular cytokine production. Subjects performed 2.5 h of cycling exercise at 65% maximal O2 uptake while ingesting a 6.4% carbohydrate (CHO) solution, 12.8% CHO solution, or a placebo. Peripheral whole blood samples were stimulated and stained for T lymphocyte surface antigens (CD4 and CD8). Cells were then permeabilized, stained for intracellular cytokines, and analyzed using flow cytometry. Exercise resulted in a decrease (P < 0.05) in the number and percentage of IFN-gamma positive CD4+ and CD8+ T lymphocytes. These stimulated cells produced less IFN-gamma immediately postexercise (P < 0.05) and 2-h postexercise (P < 0.05) compared with preexercise. However, CHO ingestion, which attenuated the exercise-induced stress hormone response compared with placebo (P < 0.05), prevented both the decrease in the number and percentage of IFN-gamma-positive CD4+ and CD8+ T lymphocytes and the suppression of IFN-gamma production from stimulated CD4+ and CD8+ T lymphocytes. There was no effect of exercise on the number of, or cytokine production from, IL-4-positive CD4+ or CD8+ T lymphocytes. These data provide support for the role of exercise-induced elevations in stress hormones in the regulation of type 1 T lymphocyte cytokine production and distribution.

Adaptation, Physiological↗
PubMed2004

Serum free light chains for monitoring multiple myeloma.

Monoclonal immunoglobulin free light chains (FLC) are found in the serum and urine of patients with a number of B-cell proliferative disorders, including multiple myeloma. Automated immunoassays, which can measure FLC in serum, are useful for the diagnosis and monitoring of light chain (AL) amyloidosis, Bence Jones myeloma and non-secretory myeloma patients. We report the results of a study investigating the utility of serum FLC measurements in myeloma patients producing monoclonal intact immunoglobulin proteins. FLC concentrations were measured in presentation sera from 493 multiple myeloma patients with monoclonal, intact immunoglobulin proteins. Serial samples were assayed from 17 of these patients and the FLC measurements were compared with other disease markers. Serum FLC concentrations were abnormal in 96% of patients at presentation. FLC concentrations fell more rapidly in response to treatment than intact immunoglobulin G (IgG) and showed greater concordance with serum beta2 microglobulin concentrations and bone marrow plasma cell assessments. It was concluded that serum FLC assays could be used to follow the disease course in nearly all multiple myeloma patients. In addition, because of their short serum half-life, changes in serum FLC concentrations provide a rapid indication of the response to treatment.

Biomarkers↗
PubMed2003

Fibrates and medroxyprogesterone acetate induce apoptosis of primary Burkitt's lymphoma cells and cell lines: potential for applying old drugs to a new disease.

Current therapies for Burkitt's lymphoma (BL) utilise combined cytotoxic chemotherapy, but these treatments are not always available in areas where the disease is endemic and are also markedly less successful in AIDS-related BL. Therefore, additional therapies are urgently required. We demonstrate here that combined fibrates and MPA exert powerful, antiproliferative actions against well-characterised Daudi, Raji and L3055 BL cell lines and primary BL cells. Detailed studies in L3055 demonstrated that this activity was mediated by induced apoptosis and confirmed by observations that overexpression of the antiapoptotic genes bcl-2 or bcl-x(L) conferred significant protection against the drugs. Importantly, since fibrates and MPA are inexpensive and stable with minimal-associated toxicities, we suggest that these drugs should be considered as adjuncts to currently available treatments for BL in endemic and AIDS-related disease.

Antineoplastic Agents, Hormonal↗
PubMed2001

Cell proliferation and CD11b expression are controlled independently during HL60 cell differentiation initiated by 1,25 alpha-dihydroxyvitamin D(3) or all-trans-retinoic acid.

When 1 alpha,25-dihydroxyvitamin D(3) (D(3)) induces HL60 cells to differentiate to monocytes, a burst of approximately three shortened cell cycles ("maturation divisions") precedes exit from cell cycle and completion of maturation. Here we show that similar maturation divisions occur during neutrophil differentiation induced by all-trans-retinoic acid (ATRA), but without shortening of the cell cycle. Both ATRA and D(3) initiate these maturation divisions as cells pass through a "window of sensitivity" during early G1. We also investigated whether the initiation of maturation divisions and of the expression of CD11b, an early-expressed maturation marker, are linked. Cells treated with D(3) or ATRA start to express CD11b after 9--14 h, before completing the first maturation division. Elutriation was used to isolate small HL60 cells (almost all in G1) and larger cells (in G1 and S phases) from unsynchronized populations. When these were cultured with D(3) or ATRA, most reentered cycle synchronously, multiplied, and differentiated. Following D(3) treatment, the G1-enriched small cells expressed CD11b slightly faster than unsynchronized cultures or fractions dominated by late G1 cells and/or S phase cells. D(3)-induced CD11b expression occurred at a similar rate even in G1 cells that were held at the G1/S boundary by thymidine. In conclusion, changes in the control of the cell cycle that characterize the onset of monocytic and neutrophil differentiation are only triggered in early G1, but CD11b expression can be initiated from most points in the cell cycle. Differentiating agents must therefore regulate the proliferation and the maturation of differentiating myeloid cells by mechanisms that are at least partly independent.

Antineoplastic Agents↗
PubMed2001

Long-term follow-up of a prospective, double-blind, placebo-controlled randomized trial of clodronate in multiple myeloma.

Oral clodronate (1600 mg/d) has been shown to significantly reduce the incidence of skeletal complications in multiple myeloma. Preliminary analysis of a double-blind placebo-controlled trial of this treatment indicated that clodronate might prolong survival in patients without vertebral fractures at presentation. This issue was re-examined after further follow-up of the patients recruited into the Medical Research Council (MRC) VIth Myeloma Study. The trial examined the effects of clodronate on the natural history of skeletal disease in multiple myeloma; 619 patients were randomized between June 1986 and May 1992 commencing 15 d after the start of ABCM [adriamycin, BCNU (carmustine), cyclophosphamide, melphalan] chemotherapy or 43 d after ABCMP (ABCM + prenisolone); 535 patients who received clodronate or placebo were included in the analysis. The presence or absence of spinal fractures was assessed centrally from spinal X-rays; long-bone fractures were assessed locally. With a median follow-up of 8.6 years, there was no overall significant difference in survival between the two treatment groups (O/E, chi2 = 0.78, P = 0.38). Among the subgroup of 153 patients with no skeletal fractures at presentation there was a significant survival advantage (O/E, chi2 = 7.52, P = 0.006) in favour of the 73 patients receiving clodronate, with median survivals being, respectively, 59 months (95% CI 43-71 months) and 37 months (95% CI 31-52 months), and 5-year survivals being 46% and 35%. The original analysis of this study shows that there is a benefit in taking 1600 mg clodronate daily for patients with myelomatosis to prevent the development of new skeletal disease. Bearing in mind the limitations of subgroup analysis, the present study indicates that treatment may prolong survival in patients without overt skeletal disease at diagnosis. These observations, however, require confirmation in prospective clinical trials.

Aged↗
PubMed2001

Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine.

BACKGROUND: Bence Jones proteins or monoclonal immunoglobulin kappa and lambda free light chains (FLCs) are important markers for identifying and monitoring many patients with B-cell tumors. Automated immunoassays that measure FLCs in urine and serum have considerable clinical potential. METHODS: Sheep antibodies, specific for FLCs, were prepared by immunization with pure kappa and lambda molecules and then adsorbed extensively against whole immunoglobulins. The antibodies were conjugated onto latex particles and used to assay kappa and lambda FLCs on the Beckman IMMAGE protein analyzer. RESULTS: The unconjugated antibodies showed minimal cross-reactivity with intact immunoglobulins or other proteins. With latex-conjugated antibodies, kappa and lambda FLCs could be measured in normal sera and most normal urine samples. Patients with multiple myeloma had increased concentrations of the relevant serum FLC, whereas both FLCs were increased in the sera of patients with systemic lupus erythematosus. CONCLUSIONS: We developed sensitive, automated immunoassays for kappa and lambda FLC measurements in serum and urine that should facilitate the assessment of patients with light chain abnormalities.

Animals↗
PubMed1999

Monocytically differentiating HL60 cells proliferate rapidly before they mature.

1alpha,25-Dihydroxyvitamin D(3) (D(3)) provokes growth arrest and monocytic differentiation in myeloid cells. Although it is usually assumed that the cellular events leading to growth arrest start within one cell cycle of D(3) addition, there is also evidence that D(3) provokes the expression of proliferation-related genes and accelerates cell division. Herein we clarify the relationship between proliferation and maturation in differentiating HL60 cells. Cells were cultured singly, D(3) was added at various stages of the cell cycle, the progeny were counted, and the proportions of mature monocytes were determined. Initially, the D(3)-treated cells proliferated at an accelerated rate, and they matured only later. If cells encountered D(3) early in G1 they divided two to four times before maturing, and if they encountered D(3) later in the cell cycle they underwent an extra division. Indomethacin slows HL60 cell multiplication by prolonging G1, and when these slower-growing cells were exposed to D(3), they matured after the usual period but underwent one division less than indomethacin-free cells. Contrary to common assumptions, we conclude that promyeloid cells do not initiate growth arrest or monocytic maturation immediately after exposure to D(3). Instead, an encounter with D(3) early in G1 sets in train a complex differentiation program. This consists of 2-3 days of rapid proliferation-probably employing cell cycles with a shortened G1 phase-that is followed by growth arrest and maturation. As a result, a single D(3)-treated promyeloid cell gives rise to 10 or more mature monocytes. These observations not only explain why "differentiating" cells express proliferation-related characteristics soon after D(3) addition, but they also show that the process of D(3)-induced monocytic differentiation is much more complex than has previously been realized.

Anti-Inflammatory Agents↗
PubMed1999

Metabolism of 1alpha,25(OH)2D3 and its 20-epi analog integrates clonal expansion, maturation and apoptosis during HL-60 cell differentiation.

Induction of growth arrest and monocyte differentiation of HL-60 leukemia cells by 1alpha,25 dihydroxyvitamin D3 (1alpha,25(OH)2D3) is well established. By contrast, we have observed, that 1alpha,25(OH)2D3 and its metabolites play separate roles in clonal expansion and survival of differentiating HL-60 cells. Cells that had differentiated by 48 h (CD14 positive) grew slower than control cells, whereas CD14 negative cells were growing faster at this time point. Inhibiting 1alpha,25(OH)2D3 or 1alpha,25(OH)2-20-epi-D3 metabolism, by the 25(OH)D3-24-hydroxylase inhibitor ketoconazole, abolished hyperproliferation of CD14 negative cells. Instead, both the onset of differentiation and subsequent apoptosis were enhanced. These events were associated with immediate up-regulation of the cyclin-dependent kinase inhibitor p21(waf1) and a lack of sustained expression, respectively. Stimulation and inhibition of growth by vitamin D3-related compounds was observed to be concentration and metabolite specific. Low amounts of 1alpha,25(OH)2-20-epi-D3 and 1alpha,24,25(OH)3-20-epi-D3 stimulated HL-60 cell growth. At higher concentrations, 1alpha,25(OH)2-20-epi-D3 was a more potent inducer than 1alpha,24,25(OH)3-20-epi-D3 of HL-60 differentiation; 1alpha,25(OH)2-20-epi-24-oxo-D3 was exclusively pro-differentiative at all concentrations. 1alpha,25(OH)2-20-epi-D3 and 1alpha,24,25(OH)3-20-epi-D3 stimulated proliferation of KG-1a leukemia cells, but neither of these compounds nor 1alpha,25(OH)3-20-epi-24-oxo-D3 exerted pro-differentiative effects on these cells. These findings shed new light on the pro- and anti-proliferative effects of 1alpha,25(OH)2D3 and lead to the postulate that metabolism of 1alpha,25(OH)2D3 and its 20-epi analog regulates different subsets of genes so as to co-ordinate population expansion and the differentiation process. Furthermore, 1alpha,25(OH)2D3 metabolism and/or sensitivity to the effects of metabolites may be altered in transformed cells to derive a clonal advantage.

Apoptosis↗
PubMed1999

Estrone potentiates myeloid cell differentiation: a role for 17 beta-hydroxysteroid dehydrogenase in modulating hemopoiesis.

Hormones such as 1 alpha, 25-dihydroxy vitamin D3 (D3), all-trans retinoic acid, and 9-cis retinoic acid stimulate differentiation of myeloid progenitor cells via their interaction with specific hormone receptors. However, the sensitivity of cells to these agents is not merely governed by the expression of their receptors and the availability of ligand to bind them. Recent studies from our group suggested that the actions of D3 and retinoids on myelopoiesis also are influenced by endogenous mechanisms involving other steroid hormones. In this study we examined the influence of local estrogen metabolism on the differentiation of HL60 cells and normal primitive myeloid progenitor cells. Quantitative thin-layer chromatography (TLC) analyses showed that HL60 and normal cells are able to generate estrone (E1) from estradiol (E2). Neither cell population generated significant amounts of E2 from E1. Reverse transcriptase polymerase chain reaction and Northern analyses confirmed that normal and leukemic myeloid progenitor cells expressed mRNA for the type I and IV isoforms of 17 beta-hydroxysteroid dehydrogenase. Conversion of E2 to E1 was upregulated within 24 hours when HL60 cells were treated with either all-trans retinoic acid or D3 at doses that induce their differentiation toward neutrophils or monocytes, respectively. Similarly, D3-induced monocyte differentiation of normal myeloid progenitor cells was associated with increased capacity to generate E1 from E2. When HL60 cells or normal myeloid progenitor cells were exposed to exogenous E1 they became more sensitive to the differentiation-inducing effects of D3. Data presented provide further evidence for the local modulation of myelopoiesis by intracrine mechanisms. In particular, our findings suggest that local metabolism of steroids by normal as well as leukemic myeloid cells influences their responsiveness to D3 and retinoids.

17-Hydroxysteroid Dehydrogenases↗
PubMed1999

Clofibric acid: a potential therapeutic agent in AML and MDS.

Differentiation therapy using retinoic acids (RAs) or 1alpha25-dihydroxyvitamin D3 (D3) is an attractive alternative to chemotherapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). However, with the exception of RA therapy for acute promyelocytic leukaemia (APL), RAs and D3 are not potent enough at doses that can be tolerated by patients. We demonstrate that clofibric acid (CA) enhances the response of HL60 cells to all-trans RA and D3. Our findings and those of others in the field lead us to suggest that combination therapy using all-trans RA and CA should be considered as potential therapy for AML and MDS.

Aged↗
PubMed1998

A randomized trial of the effect of clodronate on skeletal morbidity in multiple myeloma. MRC Working Party on Leukaemia in Adults.

In patients with multiple myeloma, despite a major reduction of bone pain achieved with chemotherapy, skeletal disease continues to progress. The effects of clodronate, an inhibitor of osteoclastic bone resorption, are evaluated on the natural history of skeletal disease in patients with newly diagnosed multiple myeloma. Within the framework of the VIth MRC Multiple Myeloma Trial, 536 patients (218 women, 318 men) with recently diagnosed multiple myeloma were randomized to receive either clodronate 1600 mg daily (n=264) or an outwardly identical placebo (n=272) in addition to chemotherapy. Treatment with clodronate was associated with a 50% decrease in the proportion of patients with severe hypercalcaemia (5.1% v 10.1%, P=0.06) and a similar reduction in reported non-vertebral fractures (6.8% v 13.2%, P=0.04). Fewer patients receiving clodronate sustained vertebral fractures after entry to the trial (38% v 55%, P=0.01) and patients also lost less height over 3 years compared to those receiving placebo (2.0 v 3.4 cm, P=0.01). Biochemical indices of bone turnover were significantly lower in patients receiving concomitant clodronate, both at plateau and at disease relapse. The frequencies of back pain and poor performance status were significantly lower at 24 months in clodronate than in placebo-treated patients (10.9% v 19.9%, P=0.05, and 18.3% v 30.5% P=0.03 respectively.) There was no statistically significant difference in survival between the clodronate and placebo treated patients. The study indicates that long-term oral clodronate slows the progression of skeletal disease in multiple myeloma and decreases the associated morbidity. Patients without overt skeletal disease at diagnosis were also found to benefit from clodronate, indicating that this treatment should be initiated as early in the course of the disease as possible.

Aged↗
PubMed1998

MRC trial of alpha2b-interferon maintenance therapy in first plateau phase of multiple myeloma. MRC Working Party on Leukaemia in Adults.

Plateau phase has been achieved in 64% of all newly diagnosed patients with multiple myeloma treated with the ABCM (adriamycin, BiCNU, cyclophosphamide and melphalan) regimen in the Medical Research Council (MRC) trials; this stable clinical stage of the disease is associated with no more than minimal symptoms. Several studies have found that alpha-interferon (alpha-IFN) maintenance therapy increases the duration of plateau phase, but it is less clear if this translates into prolonged survival. We report the effect of alpha-IFN on the duration of plateau phase and overall survival in a trial with 284 patients who were randomized to receive alpha2b-IFN (Intron-A) or no maintenance therapy during first plateau phase. The minimum follow-up after randomization was 21 months. There was no significant difference in the overall survival between the two treatment groups (X2=0.32, P=0.57). There was a trend towards longer relapse-free survival in the patients allocated alpha-IFN, but this trend to longer plateau phase was not statistically significant (X2 = 1.62, P = 0.2). Disease progression at relapse on alpha-IFN appears to be more severe with greater elevations from plateau levels of serum paraprotein (P = 0.06) and beta2-microglobulin (P= 0.03) levels. Physicians tended to start chemotherapy sooner after diagnosis of relapse when patients had received alpha-IFN (P = 0.16). Although, in common with most other studies, there is a trend for patients treated with alpha-IFN to have a longer plateau phase, this is counteracted by morbidity attributable to the treatment and a somewhat shortened survival post relapse. Meta-analysis of interferon trials is required to assess whether the minor trend for longer survival in patients maintained on alpha-IFN found in some studies is significant and, if so, the extent of this advantage.

Adult↗
PubMed1998

Renal impairment in myeloma: time for a reappraisal?

It is generally considered that a patient with myeloma who also has established renal impairment is unlikely to do well. While this is sometimes the case, analysis of recent data shows: (a) of 2768 patients in the MRC database for the fourth to the sixth trials, 10/163 with serum creatinine 300-600 microm/l and 20/89 with serum creatinine 600 micro/l at presentation had renal failure as a recorded presenting feature, whatever the renal function, the most common presenting feature was bone pain; (b) that many patients have persisting evidence of reduced renal function yet survive for more than the median time of 36 months which applies to myeloma generally. Patients with renal impairment, especially those whose myeloma is brought to plateau by chemotherapy, should be assessed thoroughly for evidence of other than myeloma induced renal damage as both renovascular disease and prostatic obstruction in males are common in the elderly population at risk.

Adult↗
PubMed1997

Triiodothyronine blocks potentiation of HL60 monocyte differentiation by anti-inflammatory agents and by steroids and induces apoptosis of all-trans retinoic acid "primed" cells.

Sensitivity of the human promyeloid cell line HL60 to physiological differentiating agents [e.g. all-trans retinoic acid (all-trans RA) and 1 alpha, 25-dihydroxyvitamin (D3)] is increased by exposure of cells to "anti-inflammatory agents" (e.g. indomethacin) and to steroids [e.g. medroxyprogesterone acetate (MPA)] and post "priming" with a low dose (10(-8) M) of all-trans RA. Co-treatment of serum free-grown HL60 cells (HL60-ITS) with indomethacin and D3 reduces the dose of D3 required for monocyte differentiation from 10(-7) to 6.25 x 10(-9) M. This potentiating effect was observed to be almost absent when experiments where undertaken using serum-grown HL60 cells (HL60-FCS). The agent present in serum that interferes with indomethacin- and MPA-potentiation of the sensitivity of HL60 cells to D3 has been identified as the thyroid hormone 3,5,3'-L-triiodothyronine (T3). "Priming" of HL60-ITS cells with a low dose of all-trans RA reduces the amount of D3 required for the induction of monocyte differentiation to the same degree as co-treatment with either indomethacin or MPA (to 5 x 10(-9) M). However, the combined effect of all-trans RA "priming" and T3 treatment of HL60-ITS cells was induction of apoptosis. Treatment with either agent alone did not result in increased levels of apoptotic cells. These data reveal that T3 has an important influence on the capacity of HL60 cells to undergo differentiation and can promote apoptosis of these cells. Drug combinations, such as a differentiation potentiating agent, for example, indomethacin or MPA, and a differentiation inducer, for example, all-trans RA or D3, may have important therapeutic significance. Serum levels of T3 would be anticipated to influence the outcome.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Complement and the recruitment of mononuclear osteoclasts.

AIM: To investigate the hypothesis that complement mediates the recruitment of mononuclear osteoclast precursors to the exposed mineralised bone surface. METHODS: Synthetic hydroxyapatite was incubated in vitro with fresh human serum, with and without complement activation inhibitors. Assays for complement components and the generation of the C3 breakdown product C3d were done. C3 deposition in human fetal tibia primary spongiosa was localised immunohistochemically and complement receptors CR1, CR2, CR3, and CR4 were localised cellularly. Immunohistochemical and enzyme histochemical characterisation of the mononuclear and multinuclear osteoclasts was made with emphasis on their association with complement C3 deposition. RESULTS: Components of complement bind to synthetic hydroxyapatite crystals and, at lower concentrations, C3d was generated in the fluid phase. C3 was deposited in a focal and linear distribution on newly formed bone trabecular surfaces in the primary spongiosa. In a similar distribution CD61, CD68, and tartrate resistant acid phosphatase positive mononuclear osteoclasts were shown in close apposition to the bone trabecular surface. These mononuclear osteoclasts, unlike multinucleate osteoclasts, expressed the complement receptors CR3 and CR4. CR1 and CR2, however, could not be shown on either mononuclear or multinuclear osteoclasts. CONCLUSION: It is suggested that C3 deposition on mineralised bone surfaces mediates the recruitment of mononuclear osteoclasts to this site. As the mononuclear osteoclasts fuse to form the multinucleate osteoclast, complement receptor expression is lost.

Bone Development↗